Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation(allo-HSCT)has been widely implemented to treat hematologic malignancies.However,graft-versus-host d...Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation(allo-HSCT)has been widely implemented to treat hematologic malignancies.However,graft-versus-host disease(GVHD)and complications of immunosuppressive drugs after allo-HSCT are the main causes of non-relapse mortality and a poor quality of life.In addition,GVHD and infusion-induced toxicity still occur with donor lymphocyte infusions(DLIs)and chimeric antigen receptor(CAR)T-cell therapy.Because of the special immune tolerance characteristics and anti-tumor ability of universal immune cells,universal immune cell therapy may strongly reduce GVHD,while simultaneously reducing tumor burden.Nevertheless,widespread application of universal immune cell therapy is mainly restricted by poor expansion and persistence efficacy.Many strategies have been applied to improve universal immune cell proliferation and persistence efficacy,including the use of universal cell lines,signaling regulation and CAR technology.In this review we have summarized current advances in universal immune cell therapy for hematologic malignancies with a discussion of future perspectives.展开更多
We have found that the expression of ring finger and WD repeat domain 3(RFWD3)is significantly higher in unpaired and paired hepatocellular carcinoma(HCC)tissues than in normal tissues.Moreover,this expression has a s...We have found that the expression of ring finger and WD repeat domain 3(RFWD3)is significantly higher in unpaired and paired hepatocellular carcinoma(HCC)tissues than in normal tissues.Moreover,this expression has a significant correlation with the infiltration level of 14 immune cell types and when the detected RFWD3 expression levels were grouped as high and low,a prominent difference was revealed for overall survival,disease-specific survival,and progression-free interval.Through statistical analysis(univariate Cox),we were also able to identify RFWD3 as an independent prognostic element for HCC,with RFWD3 having an ability to accurately predict HCC prognosis(area under the curve of 0.863).Finally,we have generated prognostic nomograms for probabilities of 1-,3-and 5-year overall survival in HCC via integrating the factors of age,pathologic stage,alpha-fetoprotein level,and RFWD3 expression.展开更多
Organ transplant rejection(OTR)is a complex immune reaction involving multiple cells,and it determines graft survival and patient prognosis.At present,most transplant recipients are administered a combination of immun...Organ transplant rejection(OTR)is a complex immune reaction involving multiple cells,and it determines graft survival and patient prognosis.At present,most transplant recipients are administered a combination of immunosuppressive and biological agents to protect them from OTR.However,immunosuppressive agents negatively impact the immune system of the patients,causing them to suffer from serious complications,such as chronic infection and malignant tumors.Therefore,a thorough understanding of the mechanisms involved in immune tolerance and immune rejection with regard to organ transplant(OT)is essential for developing better treatment options and improving patient outcomes.This article reviews the role of immune cells in OTR and organ transplant tolerance(OTT),including the novel cell therapies that are currently under clinical trials for transplant recipients.展开更多
Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in the United States and other developed countries and is expected to increase in the next few years. Emerging data suggest that some p...Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in the United States and other developed countries and is expected to increase in the next few years. Emerging data suggest that some patients with NAFLD may progress to nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma. NAFLD can also promote the development and progression of disease in other organ systems, such as the cardiovascular and endocrine (i.e. diabetes) systems. Thus, understanding the pathogenesis of NAFLD is of great clinical importance and is critical for the prevention and treatment of the disease. Although the "two-hit hypothesis" is generally accepted, the exact pathogenesis of NAFLD has not been clearly established. The liver is an important innate immune organ with large numbers of innate immune cells, including Kupffer cells (KCs), natural killer T (NKT) cells and natural killer (NK) cells. Recent data show that an imbalance in liver cytokines may be implicated in the development of fatty liver disease. For example, Th1 cytokine excess may be a common pathogenic mechanism for hepatic insulin resistance and NASH. Innate immune cells in the liver play important roles in the excessive production of hepatic Th1 cytokines in NAFLD. In addition, liver innate immune cells participate in the pathogenesis of NAFLD in other ways. For example, activated KCs can generate reactive oxygen species, which induce liver injury. This review will focus primarily on the possible effect and mechanism of KCs, NKT cells and NK cells in the development of NAFLD.展开更多
Atherosclerosis is a chronic inflammatory disease arising from lipids, specifically low-density lipoproteins, and leukocytes. Following the activation of endothelium with the expression of adhesion molecules and monoc...Atherosclerosis is a chronic inflammatory disease arising from lipids, specifically low-density lipoproteins, and leukocytes. Following the activation of endothelium with the expression of adhesion molecules and monocytes, inflammatory cytokines from macrophages, and plasmacytoid dendritic cells, high levels of interferon(IFN)-α and β are generated upon the activation of tolllike receptor-9, and T-cells, especially the ones with Th1 profile, produce pro-inflammatory mediators such as IFN-γ and upregulate macrophages to adhere to the endothelium and migrate into the intima. This review presents an exhaustive account for the role of immunecells in the atherosclerosis.展开更多
The programmed cell death-1(PD-1)/programmed cell death ligand 1(PD-L1)signaling pathway is an important mechanism in tumor immune escape,and expression of PD-L1 on tumor cells has been reported more frequently.Howeve...The programmed cell death-1(PD-1)/programmed cell death ligand 1(PD-L1)signaling pathway is an important mechanism in tumor immune escape,and expression of PD-L1 on tumor cells has been reported more frequently.However,accumulating evidence suggests that PD-1/PD-L1 is also widely expressed on immune cells,and that regulation is also critical for tumor immune responses.In this review,we emphasized that under solid tumor conditions,the immunoregulatory effects of immune cells expressing PD-1 or PD-L1,affected the prognoses of cancer patients.Therefore,a better understanding of the mechanisms that regulate PD-1 or PD-L1 expression on immune cells would provide clear insights into the increased efficacy of anti-PD antibodies and the development of novel tumor immunotherapy strategies.展开更多
Objective:Patients with non–small cell lung cancer(NSCLC)respond differently to cytokine-induced killer cell(CIK)treatment.Therefore,potential prognostic markers to identify patients who would benefit from CIK treatm...Objective:Patients with non–small cell lung cancer(NSCLC)respond differently to cytokine-induced killer cell(CIK)treatment.Therefore,potential prognostic markers to identify patients who would benefit from CIK treatment must be elucidated.The current research aimed at identifying predictive prognostic markers for efficient CIK treatment of patients with NSCLC.Methods:Patients histologically diagnosed with NSCLC were enrolled from the Tianjin Medical University Cancer Institute and Hospital.We performed whole-exome sequencing(WES)on the tumor tissues and paired adjacent benign tissues collected from 50 patients with NSCLC,and RNA-seq on tumor tissues of 17 patients with NSCLC before CIK immunotherapy treatment.Multivariate Cox proportional hazard regression analysis was used to analyze the association between clinical parameters and prognostic relevance.WES and RNA-seq data between lung squamous cell carcinoma(SCC)and adenocarcinoma(Aden)were analyzed and compared.Results:The pathology subtype of lung cancer was the most significantly relevant clinical parameter associated with DFS,as analyzed by multivariate Cox proportional hazard regression(P=0.031).The patients with lung SCC showed better CIK treatment efficacy and extended DFS after CIK treatment.Relatively low expression of HLA class II genes and checkpoint molecules,and less immunosuppressive immune cell infiltration were identified in the patients with lung SCC.Conclusions:Coordinated suppression of the expression of HLA class II genes and checkpoint molecules,as well as less immune suppressive cell infiltration together contributed to the better CIK treatment efficacy in lung SCC than lung Aden.展开更多
BACKGROUND Immune cells,including neutrophils,natural killer(NK)cells,T cells,NKT cells and macrophages,participate in the progression of acute liver injury and hepatic recovery.To date,there has been no systematic st...BACKGROUND Immune cells,including neutrophils,natural killer(NK)cells,T cells,NKT cells and macrophages,participate in the progression of acute liver injury and hepatic recovery.To date,there has been no systematic study on the quantitative changes in these different immune cells from initial injury to subsequent recovery.AIM To investigate the infiltration changes of various immune cells in acute liver injury models over time,and to study the relationship between the changes in leukocyte cellderived chemotaxin 2(LECT2)and the infiltration of several immune cells.METHODS Carbon tetrachloride-and concanavalin A-induced acute liver injury models were employed to mimic toxin-induced and autoimmune-mediated liver injury respectively.The quantitative changes in various immune cells were monitored at different time points.Serum samples were collected,and liver tissues were harvested.Ly6G,CD161,CD4,CD8 and F4/80 staining were used to indicate neutrophils,NK/NKT cells,CD4^(+)T cells,CD8^(+)T cells and macrophages,respectively.Lect2-KO mice were used to detect the function of LECT2.RESULTS During the injury and repair process,different types of immune cells began to increase,reached their peaks and fell into decline at different time points.Furthermore,when the serum alanine transaminase(ALT)and aspartate transaminase(AST)indices reverted to normal levels 7 d after the injury,the infiltration of immune cells still existed even 14 d after the injury,showing an obvious lag effect.We found that the expression of LECT2 was upregulated in acute liver injury mouse models,and the liver injuries of Lect2-KO mice were less severe than those of wild-type mice.Compared with wild-type mice,Lect2-KO mice had different immune cell infiltration.CONCLUSION The recovery time of immune cells was far behind that of serum ALT and AST during the process of liver repair.LECT2 could regulate monocyte/macrophage chemotaxis and might be used as a therapeutic target for acute liver injury.展开更多
Objective:The aim of this study was to identify hub genes associated with immune cell infiltration in breast cancer through bioinformatic analyses of multiple datasets.Methods:Nonparametric(NOISeq)and robust rank aggr...Objective:The aim of this study was to identify hub genes associated with immune cell infiltration in breast cancer through bioinformatic analyses of multiple datasets.Methods:Nonparametric(NOISeq)and robust rank aggregation-ranked parametric(EdgeR)methods were used to assess robust differentially expressed genes across multiple datasets.Protein-protein interaction network,GO,KEGG enrichment,and subnetwork analyses were performed to identify immune-associated hub genes in breast cancer.Immune cell infiltration was evaluated with the CIBERSORT,XCELL,and TIMER methods.The association between the hub gene-based risk signature and survival was determined through Kaplan–Meier survival analysis,multivariate Cox analysis,and a nomogram with external verification.Results:We identified 163 robust differentially expressed genes in breast cancer through applying both nonparametric and parametric methods to multiple GEO(n=2,212)and TCGA(n=1,045)datasets.Integrated bioinformatic analyses further identified 10 hub genes:CXCL10,CXCL9,CXCL11,SPP1,POSTN,MMP9,DPT,COL1A1,ADAMDEC1,and RGS1.The 10 hub-gene-based risk signature significantly correlated with the prognosis of patients with breast cancer.Moreover,these hub genes were strongly associated with the extent of infiltration of CD4+T cells,CD8+T cells,neutrophils,macrophages,and myeloid dendritic cells into breast tumors.Conclusions:Integrated analyses of multiple databases led to the discovery of 10 robust hub genes that together may serve as a risk factor characteristic of the immune microenvironment in breast cancer.展开更多
Acute myeloid leukemia(AML)is regarded as a stem cell disease.However,no one unique marker is expressed on leukemia stem cells(LSC)but not on leukemic blasts nor normal hematopoietic stem cells(HSC).CD34^(+)CD38^(-)wi...Acute myeloid leukemia(AML)is regarded as a stem cell disease.However,no one unique marker is expressed on leukemia stem cells(LSC)but not on leukemic blasts nor normal hematopoietic stem cells(HSC).CD34^(+)CD38^(-)with or without CD123 or CD44 subpopulations are immunophenotypically defined as putative LSC fractions in AML.Nevertheless,markers that can be effectively and simply held responsible for the intrinsical heterogeneity of LSC is still unclear.In the present study,we examined the frequency of three different LSC subtypes(CD34^(+)CD38^(-),CD34^(+)CD38^(-)CD123^(+),CD34^(+)CD38^(-)CD44^(+))in AML at diagnosis.We then validated their prognostic significance on the relevance of spectral features for diagnostic stratification,immune status,induction therapy response,treatment effect maintenance,and long^(-)term survival.In our findings,high proportions of the above three different LSC subtypes were all significantly characterized with low complete remission(CR)rate,high relapse/refractory rate,poor overall survival(OS),frequent FLT3^(-)ITD mutation,the high level of regulatory T cells(Treg)and monocytic myeloid^(-)derived suppressor cells(M^(-)MDSC).However,there was no significant statistical difference in all kinds of other clinical performance among the three different LSC groups.It was demonstrated that CD34^(+)CD38^(-)subpopulation without CD123 and CD44 might be held responsible for LSC and correlated with an imbalance of immune cell subsets in AML.展开更多
BACKGROUND CD155 is an immune checkpoint protein in cancers and interacts with ligands to regulate the immune microenvironment.The expression of CD155 is correlated with the prognosis and pathological features of brea...BACKGROUND CD155 is an immune checkpoint protein in cancers and interacts with ligands to regulate the immune microenvironment.The expression of CD155 is correlated with the prognosis and pathological features of breast cancer.AIM To investigate the expression status of CD155 and the association with exhausted CD4+helper and CD8+cytotoxic tumor infiltrating lymphocytes(TILs)and PD-L1 in the breast cancer microenvironment.METHODS One hundred and twenty-six breast cancer patients with invasive ductal breast cancer were consecutively recruited into this study.Immunohistochemistry was used to detect the expression CD155,PD-L1 and PD-1 on tumor-infiltrating immune cells and tumor cells in the microenvironment.RESULTS The proportion of patients with CD155 expression was higher in triple negative breast cancer(72.7%)than in Luminal A patients(22.2%,P<0.05).Patients with positive CD155 expression had a higher percentage of CD4+/PD-1+helper TILs(30%)than patients with negative CD155 expression(21%,P<0.05).Patients with positive CD155 expression also had higher cell counts of exhausted CD4+TILs[47 vs 20/high-power fields(HPF)]and unexhausted CD8+TILs(30 vs 17/HPF)than patients with negative expression(P<0.05).CD155 expression was correlated with increased PD-L1 expression in immune cells,0.8%and 0.02%immune cells expressed PD-L1 in patients with positive and negative CD155 expression,respectively(P<0.05).CONCLUSION CD155 was related to an inhibitory immune breast cancer microenvironment.CD155 was associated with a high proportion of exhausted CD4+and unexhausted CD8+TILs and high PD-L1 expression in immune cells.展开更多
Objective:To investigate the correlation between immune cell infiltration pattern and clinical features and prognosis of cervical carcinoma.Methods:All cervical cancer transcript data and related clinical data were do...Objective:To investigate the correlation between immune cell infiltration pattern and clinical features and prognosis of cervical carcinoma.Methods:All cervical cancer transcript data and related clinical data were downloaded from the public database Cancer Genome Atlas(TCGA),and the relative proportions of 22 invasive immune cell types were calculated by Cibersort software.Perl was used to assess the correlation between the pattern of immune cell invasion and clinical characteristics(age,clinical stage,tumor grade)in cervical cancer,and the correlation between the pattern of immune cell invasion and survival in cervical cancer was calculated by the K-M Log-Rank method.Result:The distribution of immune cells in 306 cases of cervical cancer and 3 cases of normal tissues was assessed using Cibersort.Compared with normal tissues,the contents of resting dendritic cells,activated dendritic cells,M1 macrophages and activated CD4+memory T cells were higher;the contents of M2 macrophages,neutrophils,regulatory T cells and activated mast cells were lower in cervical cancer tissues.The contents of M1 macrophages,unactivated CD4+memory T cells,andγδT cells were positively correlated with patient age(P<0.05).The contents of follicular helper T cells,activated and unactivated natural killer(NK)cells,and naive CD4 T cells were negatively correlated with patient age(P<0.05).Those with high resting dendritic cell composition had shorter overall survival,while those with high follicular helper T cell composition had longer overall survival(P<0.05).Conclusion:Compared with normal tissues,the composition of immune cells in cervical cancer tissues has certain specificity,which can provide reference for the early screening and diagnosis of the disease.Patients in different age groups may have different immune cell infiltration patterns,which can be used as a basis to explore drug targets in clinical practice.Resting dendritic cells and follicular helper T cells in cervical cancer can be used as possible efficacy predictors of clinical immunotherapy for cervical cancer.展开更多
Brucellosis is one of the most prevalent zoonoses in the world. Incidence of the disease has increased significantly in recent years and has seriously affected the health of human beings and the development of animal ...Brucellosis is one of the most prevalent zoonoses in the world. Incidence of the disease has increased significantly in recent years and has seriously affected the health of human beings and the development of animal husbandry. The pathogenesis of brucellosis remains unclear. Current studies suggest that this disease may be related to changes in natural killer cells, dendritic cells, and macrophages in immune cell subsets. Brucellosis may be also related to T helper(Th) 1 cell/Th2 cell imbalance in the CD4^+ T cell subset, immunoregulation of regulatory T cells and Th17 cells, and the mechanism of action of CD8^+ T cell. This paper aims to review the research progress on these inherent immune cells, the CD4^+ T cell subset, and CD8^+ T cells in Brucella infection.展开更多
Many researchers have described that mesenchymal stem cells conditioned medium and immune cells conditioned medium have a clear whitening effect when they are used as cosmetic ingredients. In this study, we confirmed ...Many researchers have described that mesenchymal stem cells conditioned medium and immune cells conditioned medium have a clear whitening effect when they are used as cosmetic ingredients. In this study, we confirmed the whitening efficacy of various concentrations of immune cells and stem cell conditioned media. The author tried to study a conditioned medium that has a strong whitening effect even with a composition of less than 20% (the most used concentration in cosmetics). Because of the fact that the conditioned medium contains various cytokines and growth factors secreted by stem cells or immune cells, it is known to have effects such as wound healing, antioxidant, and whitening effect. Recently, stem cells have been used not only in the development of cosmetic raw materials but also in skincare procedures, and there are reports being released of cosmetics using immune cells conditioned medium. The concentration-dependent whitening effect equivalently increased as the concentration of the mono-cultured conditioned medium was obtained through the stem cells or immune cells culture. In the case of co-culture, whitening results are like the effect of positive control such as arbutin in the medium carrying only 10% of the co-cultured conditioned medium. It is possible that enhanced whitening efficiency in co-cultured conditioned medium leads to a major innovation in the global cosmetic market.展开更多
Background:Ferroptosis is an iron dependent form of cell death,which plays an important role in the pathogenesis of a variety of urinary malignancies.The down-regulation of DECR1 gene causes the accumulation of polyun...Background:Ferroptosis is an iron dependent form of cell death,which plays an important role in the pathogenesis of a variety of urinary malignancies.The down-regulation of DECR1 gene causes the accumulation of polyunsaturated fatty acids(PUFAs),increases the susceptibility to lipid peroxidation,and finally leads to cell death.Methods:We first searched the data to find reductase 1(DECR1)expression in bladder uroepithelial carcinoma and healthy surrounding tissues in the Cancer Genome Atlas(TCGA),and we then confirmed DECR1 expression with additional independent cohorts in the Gene Expression Omnibus(GEO)database and the Human Protein Atlas(HPA).In order to determine the link between DECR1 expression and clinical traits and overall survival(OS),as well as to create nomograms,multivariate analysis and Kaplan Meier survival curves were utilized.Through the use of an online string website,the network of proteins that interact with DECR1 was created.Through an online string website,the protein network interacting with DECR1 was built.Finally,we looked at the association between aggressive immune cells and the marker genes that belong to them and DECR1 expression.Results:When compared to normal tissues,bladder tumor tissues had higher DECR1 expression(P=0.002).Low DECR1 expression was linked with tumor grade and stage in tumor cells.BLCA patients with low DECR1 expression had a lower overall survival than BLCA patients with high DECR1 expression,according to a survival study(P=0.008).The protein network’s HSD17B4 and DECR1 connections are crucial.The expression of regulatory T cells,regulatory B cells,and their markers were decreased when DECR1 was missing in bladder cancer.Conclusion:Decreased DECR1 expression was associated with BLCA progression,poor prognosis and impaired infiltration of some immune cells.展开更多
Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered ...Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the crit...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.展开更多
Background Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children.It is associated with high rates of morbidity...Background Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children.It is associated with high rates of morbidity and mortality,and rapid detection and administration of antimicrobials have been emphasized.The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness.Methods Three gene expression datasets were available from the Gene Expression Omnibus collection.First,the differentially expressed genes(DEGs)were found with the use of the R program,and then gene set enrichment analysis was carried out.Subsequently,the DEGs were combined with the major module genes chosen using the weighted gene co-expression network.The hub genes were identified by the use of three machine-learning algorithms:random forest,support vector machine-recursive feature elimination,and least absolute shrinkage and selection operator.The receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes.In addition,the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts(CIBERSORT).The relationship between the diagnostic markers and infiltrating immune cells was further studied.Results Overall,after overlapping key module genes and DEGs,we detected 402 overlapping genes.As pediatric sepsis diagnostic indicators,CYSTM1(AUC=0.988),MMP8(AUC=0.973),and CD177(AUC=0.986)were investigated and demonstrated statistically significant differences(P<0.05)and diagnostic efficacy in the validation set.As indicated by the immune cell infiltration analysis,multiple immune cells may be involved in the development of pediatric sepsis.Additionally,all diagnostic characteristics may correlate with immune cells to varying degrees.Conclusions The candidate hub genes(CD177,CYSTM1,and MMP8)were identified,and the nomogram was constructed for pediatric sepsis diagnosis.Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.展开更多
Background:The tumor microenvironment plays an essential role in the therapeutic response to immunotherapy.It is necessary to identify immune cell infiltration(ICI)subtypes for evaluating prognosis and therapeutic ben...Background:The tumor microenvironment plays an essential role in the therapeutic response to immunotherapy.It is necessary to identify immune cell infiltration(ICI)subtypes for evaluating prognosis and therapeutic benefits.This study aimed to evaluate the ICI score as an effective prognostic biomarker for immune response.Methods:The cell-type identification by estimating relative subsets of RNA transcripts and the estimation of stromal and immune cells in malignant tumors using expression methods were used to analyse ICI landscapes in 161 colorectal cancer(CRC)samples with patients’clinical and prognostic data,RNA sequencing data,and whole-exome sequencing data from the Sixth Affiliated Hospital,Sun Yat-sen University(Guangzhou,China).Statistical analysis and data processing were conducted to calculate ICI scores,and to analyse the prognosis of CRC patients with different ICI scores and other features.A similar analysis with RNA sequencing and clinical data of colon adenocarcinoma(COAD)samples from The Cancer Genome Atlas(TCGA)database was conducted to confirm the correctness of the findings.Results:The high-ICI score group with a better prognosis(hazard ratio[HR],2.19;95%confidence interval[CI],1.03–4.64;logrank test,P=0.036)was characterized by the increased tumor mutational burden and interleukin-17(IL-17)signaling pathway.Significant differences in the prognosis and the expression levels of immune checkpoints and chemokine marker genes were found between the two ICI score groups.For COAD samples from TCGA,the results also showed a significant difference in patients’prognosis between the two ICI score groups(HR,1.72;95%CI,1.00–2.96;log-rank test,P=0.047).Conclusions:Tumor heterogeneity induced differences in identifying ICI subtypes of CRC patients.The ICI score may serve as an effective biomarker for predicting prognosis,help identify new therapeutic markers for CRC,and develop novel effective immune checkpoint blockade therapies.展开更多
基金supported by the National Key R&D Program of China(Grant No.2022YFA1103300)the National Natural Science Foundation of China(Grant No.82020108004)+3 种基金the Natural Science Foundation of Chongqing Innovation Group Science Program(Grant No.cstc2021jcyjcxttX0001)the Natural Science Foundation of Chongqing(Grant No.CSTB2022NSCQ-MSX1060)the Special Project for Talent Construction in Xinqiao Hospital(Grant No.2022XKRC001)the National College Student Innovation and Entrepreneurship Training Program(Grant No.202190035001).
文摘Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation(allo-HSCT)has been widely implemented to treat hematologic malignancies.However,graft-versus-host disease(GVHD)and complications of immunosuppressive drugs after allo-HSCT are the main causes of non-relapse mortality and a poor quality of life.In addition,GVHD and infusion-induced toxicity still occur with donor lymphocyte infusions(DLIs)and chimeric antigen receptor(CAR)T-cell therapy.Because of the special immune tolerance characteristics and anti-tumor ability of universal immune cells,universal immune cell therapy may strongly reduce GVHD,while simultaneously reducing tumor burden.Nevertheless,widespread application of universal immune cell therapy is mainly restricted by poor expansion and persistence efficacy.Many strategies have been applied to improve universal immune cell proliferation and persistence efficacy,including the use of universal cell lines,signaling regulation and CAR technology.In this review we have summarized current advances in universal immune cell therapy for hematologic malignancies with a discussion of future perspectives.
文摘We have found that the expression of ring finger and WD repeat domain 3(RFWD3)is significantly higher in unpaired and paired hepatocellular carcinoma(HCC)tissues than in normal tissues.Moreover,this expression has a significant correlation with the infiltration level of 14 immune cell types and when the detected RFWD3 expression levels were grouped as high and low,a prominent difference was revealed for overall survival,disease-specific survival,and progression-free interval.Through statistical analysis(univariate Cox),we were also able to identify RFWD3 as an independent prognostic element for HCC,with RFWD3 having an ability to accurately predict HCC prognosis(area under the curve of 0.863).Finally,we have generated prognostic nomograms for probabilities of 1-,3-and 5-year overall survival in HCC via integrating the factors of age,pathologic stage,alpha-fetoprotein level,and RFWD3 expression.
基金supported by grants from the National Natural Science Foundation of China(81971495 and 91442117)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-035)+2 种基金the National Science Foundation of Jiangsu Province(BRA2017533 and BK20191490)the State Key Laboratory of Reproductive Medicine(SKLRM-K202001)the Foundation of Jiangsu Collaborative Innovation Center of Biomedical Functional Materials。
文摘Organ transplant rejection(OTR)is a complex immune reaction involving multiple cells,and it determines graft survival and patient prognosis.At present,most transplant recipients are administered a combination of immunosuppressive and biological agents to protect them from OTR.However,immunosuppressive agents negatively impact the immune system of the patients,causing them to suffer from serious complications,such as chronic infection and malignant tumors.Therefore,a thorough understanding of the mechanisms involved in immune tolerance and immune rejection with regard to organ transplant(OT)is essential for developing better treatment options and improving patient outcomes.This article reviews the role of immune cells in OTR and organ transplant tolerance(OTT),including the novel cell therapies that are currently under clinical trials for transplant recipients.
基金Supported by Beijing Municipal Laboratory for Liver Protection and Regulation of Regeneration, Beijing, China
文摘Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in the United States and other developed countries and is expected to increase in the next few years. Emerging data suggest that some patients with NAFLD may progress to nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma. NAFLD can also promote the development and progression of disease in other organ systems, such as the cardiovascular and endocrine (i.e. diabetes) systems. Thus, understanding the pathogenesis of NAFLD is of great clinical importance and is critical for the prevention and treatment of the disease. Although the "two-hit hypothesis" is generally accepted, the exact pathogenesis of NAFLD has not been clearly established. The liver is an important innate immune organ with large numbers of innate immune cells, including Kupffer cells (KCs), natural killer T (NKT) cells and natural killer (NK) cells. Recent data show that an imbalance in liver cytokines may be implicated in the development of fatty liver disease. For example, Th1 cytokine excess may be a common pathogenic mechanism for hepatic insulin resistance and NASH. Innate immune cells in the liver play important roles in the excessive production of hepatic Th1 cytokines in NAFLD. In addition, liver innate immune cells participate in the pathogenesis of NAFLD in other ways. For example, activated KCs can generate reactive oxygen species, which induce liver injury. This review will focus primarily on the possible effect and mechanism of KCs, NKT cells and NK cells in the development of NAFLD.
文摘Atherosclerosis is a chronic inflammatory disease arising from lipids, specifically low-density lipoproteins, and leukocytes. Following the activation of endothelium with the expression of adhesion molecules and monocytes, inflammatory cytokines from macrophages, and plasmacytoid dendritic cells, high levels of interferon(IFN)-α and β are generated upon the activation of tolllike receptor-9, and T-cells, especially the ones with Th1 profile, produce pro-inflammatory mediators such as IFN-γ and upregulate macrophages to adhere to the endothelium and migrate into the intima. This review presents an exhaustive account for the role of immunecells in the atherosclerosis.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.81974416 and 81872166)the Key Project of Tianjin Health Industry(Grant No.15KG145).
文摘The programmed cell death-1(PD-1)/programmed cell death ligand 1(PD-L1)signaling pathway is an important mechanism in tumor immune escape,and expression of PD-L1 on tumor cells has been reported more frequently.However,accumulating evidence suggests that PD-1/PD-L1 is also widely expressed on immune cells,and that regulation is also critical for tumor immune responses.In this review,we emphasized that under solid tumor conditions,the immunoregulatory effects of immune cells expressing PD-1 or PD-L1,affected the prognoses of cancer patients.Therefore,a better understanding of the mechanisms that regulate PD-1 or PD-L1 expression on immune cells would provide clear insights into the increased efficacy of anti-PD antibodies and the development of novel tumor immunotherapy strategies.
基金This work was supported by the National Key Technologies R&D Program(Grant No.2015BAI12B12)the National Key R&D Program(Grant No.2018YFC1313400)+2 种基金grants from the National Natural Science Foundation of China(Grant Nos.81802873 and 81672697)the Natural Science Foundation of Tianjin(Grant No.18JCQNJC81300)the Tianjin Municipal Education Commission Program(Grant No.2017KJ197).
文摘Objective:Patients with non–small cell lung cancer(NSCLC)respond differently to cytokine-induced killer cell(CIK)treatment.Therefore,potential prognostic markers to identify patients who would benefit from CIK treatment must be elucidated.The current research aimed at identifying predictive prognostic markers for efficient CIK treatment of patients with NSCLC.Methods:Patients histologically diagnosed with NSCLC were enrolled from the Tianjin Medical University Cancer Institute and Hospital.We performed whole-exome sequencing(WES)on the tumor tissues and paired adjacent benign tissues collected from 50 patients with NSCLC,and RNA-seq on tumor tissues of 17 patients with NSCLC before CIK immunotherapy treatment.Multivariate Cox proportional hazard regression analysis was used to analyze the association between clinical parameters and prognostic relevance.WES and RNA-seq data between lung squamous cell carcinoma(SCC)and adenocarcinoma(Aden)were analyzed and compared.Results:The pathology subtype of lung cancer was the most significantly relevant clinical parameter associated with DFS,as analyzed by multivariate Cox proportional hazard regression(P=0.031).The patients with lung SCC showed better CIK treatment efficacy and extended DFS after CIK treatment.Relatively low expression of HLA class II genes and checkpoint molecules,and less immunosuppressive immune cell infiltration were identified in the patients with lung SCC.Conclusions:Coordinated suppression of the expression of HLA class II genes and checkpoint molecules,as well as less immune suppressive cell infiltration together contributed to the better CIK treatment efficacy in lung SCC than lung Aden.
基金Supported by the National Key R&D Program of ChinaNo. 2018YFA0108200 and No. 2018YFC1106400+5 种基金the National Natural Science Foundation of ChinaNo. 31972926, No. 32000607, No. 82270645 and No. 92068206Guangdong Basic and Applied Basic Research FoundationNo. 2020A1515111111 and No. 2019A1515110145China Postdoctoral Science FoundationNo. 2019M660205
文摘BACKGROUND Immune cells,including neutrophils,natural killer(NK)cells,T cells,NKT cells and macrophages,participate in the progression of acute liver injury and hepatic recovery.To date,there has been no systematic study on the quantitative changes in these different immune cells from initial injury to subsequent recovery.AIM To investigate the infiltration changes of various immune cells in acute liver injury models over time,and to study the relationship between the changes in leukocyte cellderived chemotaxin 2(LECT2)and the infiltration of several immune cells.METHODS Carbon tetrachloride-and concanavalin A-induced acute liver injury models were employed to mimic toxin-induced and autoimmune-mediated liver injury respectively.The quantitative changes in various immune cells were monitored at different time points.Serum samples were collected,and liver tissues were harvested.Ly6G,CD161,CD4,CD8 and F4/80 staining were used to indicate neutrophils,NK/NKT cells,CD4^(+)T cells,CD8^(+)T cells and macrophages,respectively.Lect2-KO mice were used to detect the function of LECT2.RESULTS During the injury and repair process,different types of immune cells began to increase,reached their peaks and fell into decline at different time points.Furthermore,when the serum alanine transaminase(ALT)and aspartate transaminase(AST)indices reverted to normal levels 7 d after the injury,the infiltration of immune cells still existed even 14 d after the injury,showing an obvious lag effect.We found that the expression of LECT2 was upregulated in acute liver injury mouse models,and the liver injuries of Lect2-KO mice were less severe than those of wild-type mice.Compared with wild-type mice,Lect2-KO mice had different immune cell infiltration.CONCLUSION The recovery time of immune cells was far behind that of serum ALT and AST during the process of liver repair.LECT2 could regulate monocyte/macrophage chemotaxis and might be used as a therapeutic target for acute liver injury.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.81874167 and 82073064).
文摘Objective:The aim of this study was to identify hub genes associated with immune cell infiltration in breast cancer through bioinformatic analyses of multiple datasets.Methods:Nonparametric(NOISeq)and robust rank aggregation-ranked parametric(EdgeR)methods were used to assess robust differentially expressed genes across multiple datasets.Protein-protein interaction network,GO,KEGG enrichment,and subnetwork analyses were performed to identify immune-associated hub genes in breast cancer.Immune cell infiltration was evaluated with the CIBERSORT,XCELL,and TIMER methods.The association between the hub gene-based risk signature and survival was determined through Kaplan–Meier survival analysis,multivariate Cox analysis,and a nomogram with external verification.Results:We identified 163 robust differentially expressed genes in breast cancer through applying both nonparametric and parametric methods to multiple GEO(n=2,212)and TCGA(n=1,045)datasets.Integrated bioinformatic analyses further identified 10 hub genes:CXCL10,CXCL9,CXCL11,SPP1,POSTN,MMP9,DPT,COL1A1,ADAMDEC1,and RGS1.The 10 hub-gene-based risk signature significantly correlated with the prognosis of patients with breast cancer.Moreover,these hub genes were strongly associated with the extent of infiltration of CD4+T cells,CD8+T cells,neutrophils,macrophages,and myeloid dendritic cells into breast tumors.Conclusions:Integrated analyses of multiple databases led to the discovery of 10 robust hub genes that together may serve as a risk factor characteristic of the immune microenvironment in breast cancer.
基金approved by the Institutional Review Board(IRB)Institutional of the Second Hospital of Anhui Medical University(No.LLSC20140009).
文摘Acute myeloid leukemia(AML)is regarded as a stem cell disease.However,no one unique marker is expressed on leukemia stem cells(LSC)but not on leukemic blasts nor normal hematopoietic stem cells(HSC).CD34^(+)CD38^(-)with or without CD123 or CD44 subpopulations are immunophenotypically defined as putative LSC fractions in AML.Nevertheless,markers that can be effectively and simply held responsible for the intrinsical heterogeneity of LSC is still unclear.In the present study,we examined the frequency of three different LSC subtypes(CD34^(+)CD38^(-),CD34^(+)CD38^(-)CD123^(+),CD34^(+)CD38^(-)CD44^(+))in AML at diagnosis.We then validated their prognostic significance on the relevance of spectral features for diagnostic stratification,immune status,induction therapy response,treatment effect maintenance,and long^(-)term survival.In our findings,high proportions of the above three different LSC subtypes were all significantly characterized with low complete remission(CR)rate,high relapse/refractory rate,poor overall survival(OS),frequent FLT3^(-)ITD mutation,the high level of regulatory T cells(Treg)and monocytic myeloid^(-)derived suppressor cells(M^(-)MDSC).However,there was no significant statistical difference in all kinds of other clinical performance among the three different LSC groups.It was demonstrated that CD34^(+)CD38^(-)subpopulation without CD123 and CD44 might be held responsible for LSC and correlated with an imbalance of immune cell subsets in AML.
基金Supported by Beijing Municipal Committee of Science and Technology,No.Z181100001718090 and Z19110006619041Beijing Municipal Administration of Hospitals,No.PX2018029Beijing Shijitan Hospital,Capital Medical University,No.2017-KF01.
文摘BACKGROUND CD155 is an immune checkpoint protein in cancers and interacts with ligands to regulate the immune microenvironment.The expression of CD155 is correlated with the prognosis and pathological features of breast cancer.AIM To investigate the expression status of CD155 and the association with exhausted CD4+helper and CD8+cytotoxic tumor infiltrating lymphocytes(TILs)and PD-L1 in the breast cancer microenvironment.METHODS One hundred and twenty-six breast cancer patients with invasive ductal breast cancer were consecutively recruited into this study.Immunohistochemistry was used to detect the expression CD155,PD-L1 and PD-1 on tumor-infiltrating immune cells and tumor cells in the microenvironment.RESULTS The proportion of patients with CD155 expression was higher in triple negative breast cancer(72.7%)than in Luminal A patients(22.2%,P<0.05).Patients with positive CD155 expression had a higher percentage of CD4+/PD-1+helper TILs(30%)than patients with negative CD155 expression(21%,P<0.05).Patients with positive CD155 expression also had higher cell counts of exhausted CD4+TILs[47 vs 20/high-power fields(HPF)]and unexhausted CD8+TILs(30 vs 17/HPF)than patients with negative expression(P<0.05).CD155 expression was correlated with increased PD-L1 expression in immune cells,0.8%and 0.02%immune cells expressed PD-L1 in patients with positive and negative CD155 expression,respectively(P<0.05).CONCLUSION CD155 was related to an inhibitory immune breast cancer microenvironment.CD155 was associated with a high proportion of exhausted CD4+and unexhausted CD8+TILs and high PD-L1 expression in immune cells.
基金Scientific research project of Hubei provincial health commission(No.WJ2019M118)。
文摘Objective:To investigate the correlation between immune cell infiltration pattern and clinical features and prognosis of cervical carcinoma.Methods:All cervical cancer transcript data and related clinical data were downloaded from the public database Cancer Genome Atlas(TCGA),and the relative proportions of 22 invasive immune cell types were calculated by Cibersort software.Perl was used to assess the correlation between the pattern of immune cell invasion and clinical characteristics(age,clinical stage,tumor grade)in cervical cancer,and the correlation between the pattern of immune cell invasion and survival in cervical cancer was calculated by the K-M Log-Rank method.Result:The distribution of immune cells in 306 cases of cervical cancer and 3 cases of normal tissues was assessed using Cibersort.Compared with normal tissues,the contents of resting dendritic cells,activated dendritic cells,M1 macrophages and activated CD4+memory T cells were higher;the contents of M2 macrophages,neutrophils,regulatory T cells and activated mast cells were lower in cervical cancer tissues.The contents of M1 macrophages,unactivated CD4+memory T cells,andγδT cells were positively correlated with patient age(P<0.05).The contents of follicular helper T cells,activated and unactivated natural killer(NK)cells,and naive CD4 T cells were negatively correlated with patient age(P<0.05).Those with high resting dendritic cell composition had shorter overall survival,while those with high follicular helper T cell composition had longer overall survival(P<0.05).Conclusion:Compared with normal tissues,the composition of immune cells in cervical cancer tissues has certain specificity,which can provide reference for the early screening and diagnosis of the disease.Patients in different age groups may have different immune cell infiltration patterns,which can be used as a basis to explore drug targets in clinical practice.Resting dendritic cells and follicular helper T cells in cervical cancer can be used as possible efficacy predictors of clinical immunotherapy for cervical cancer.
文摘Brucellosis is one of the most prevalent zoonoses in the world. Incidence of the disease has increased significantly in recent years and has seriously affected the health of human beings and the development of animal husbandry. The pathogenesis of brucellosis remains unclear. Current studies suggest that this disease may be related to changes in natural killer cells, dendritic cells, and macrophages in immune cell subsets. Brucellosis may be also related to T helper(Th) 1 cell/Th2 cell imbalance in the CD4^+ T cell subset, immunoregulation of regulatory T cells and Th17 cells, and the mechanism of action of CD8^+ T cell. This paper aims to review the research progress on these inherent immune cells, the CD4^+ T cell subset, and CD8^+ T cells in Brucella infection.
文摘Many researchers have described that mesenchymal stem cells conditioned medium and immune cells conditioned medium have a clear whitening effect when they are used as cosmetic ingredients. In this study, we confirmed the whitening efficacy of various concentrations of immune cells and stem cell conditioned media. The author tried to study a conditioned medium that has a strong whitening effect even with a composition of less than 20% (the most used concentration in cosmetics). Because of the fact that the conditioned medium contains various cytokines and growth factors secreted by stem cells or immune cells, it is known to have effects such as wound healing, antioxidant, and whitening effect. Recently, stem cells have been used not only in the development of cosmetic raw materials but also in skincare procedures, and there are reports being released of cosmetics using immune cells conditioned medium. The concentration-dependent whitening effect equivalently increased as the concentration of the mono-cultured conditioned medium was obtained through the stem cells or immune cells culture. In the case of co-culture, whitening results are like the effect of positive control such as arbutin in the medium carrying only 10% of the co-cultured conditioned medium. It is possible that enhanced whitening efficiency in co-cultured conditioned medium leads to a major innovation in the global cosmetic market.
文摘Background:Ferroptosis is an iron dependent form of cell death,which plays an important role in the pathogenesis of a variety of urinary malignancies.The down-regulation of DECR1 gene causes the accumulation of polyunsaturated fatty acids(PUFAs),increases the susceptibility to lipid peroxidation,and finally leads to cell death.Methods:We first searched the data to find reductase 1(DECR1)expression in bladder uroepithelial carcinoma and healthy surrounding tissues in the Cancer Genome Atlas(TCGA),and we then confirmed DECR1 expression with additional independent cohorts in the Gene Expression Omnibus(GEO)database and the Human Protein Atlas(HPA).In order to determine the link between DECR1 expression and clinical traits and overall survival(OS),as well as to create nomograms,multivariate analysis and Kaplan Meier survival curves were utilized.Through the use of an online string website,the network of proteins that interact with DECR1 was created.Through an online string website,the protein network interacting with DECR1 was built.Finally,we looked at the association between aggressive immune cells and the marker genes that belong to them and DECR1 expression.Results:When compared to normal tissues,bladder tumor tissues had higher DECR1 expression(P=0.002).Low DECR1 expression was linked with tumor grade and stage in tumor cells.BLCA patients with low DECR1 expression had a lower overall survival than BLCA patients with high DECR1 expression,according to a survival study(P=0.008).The protein network’s HSD17B4 and DECR1 connections are crucial.The expression of regulatory T cells,regulatory B cells,and their markers were decreased when DECR1 was missing in bladder cancer.Conclusion:Decreased DECR1 expression was associated with BLCA progression,poor prognosis and impaired infiltration of some immune cells.
基金partially supported by the Natural Science Foundation of Zhejiang Province(Award number:D21C170001)the National Natural Science Foundation of China(Award number:31973000)。
文摘Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.
基金Supported by National Natural Foundation of China,No.821742232019 Chinese and Western Medicine Clinical Collaborative Capacity Building Project for Major Difficult Diseases,No.2019-ZX-005。
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.
基金supported by the Key R&D Program of Zhejiang(2022C03163 to X.F.).National Key Research and Development Program of China(2018YFC2001905 to X.A.)+1 种基金the National Natural Science Foundation of China(NSFC)(82230074 to X.F.,82072221 to K.Z.)the Natural Science Foundation of Zhejiang Province(LZ22H150002 to K.Z.).
文摘Background Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children.It is associated with high rates of morbidity and mortality,and rapid detection and administration of antimicrobials have been emphasized.The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness.Methods Three gene expression datasets were available from the Gene Expression Omnibus collection.First,the differentially expressed genes(DEGs)were found with the use of the R program,and then gene set enrichment analysis was carried out.Subsequently,the DEGs were combined with the major module genes chosen using the weighted gene co-expression network.The hub genes were identified by the use of three machine-learning algorithms:random forest,support vector machine-recursive feature elimination,and least absolute shrinkage and selection operator.The receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes.In addition,the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts(CIBERSORT).The relationship between the diagnostic markers and infiltrating immune cells was further studied.Results Overall,after overlapping key module genes and DEGs,we detected 402 overlapping genes.As pediatric sepsis diagnostic indicators,CYSTM1(AUC=0.988),MMP8(AUC=0.973),and CD177(AUC=0.986)were investigated and demonstrated statistically significant differences(P<0.05)and diagnostic efficacy in the validation set.As indicated by the immune cell infiltration analysis,multiple immune cells may be involved in the development of pediatric sepsis.Additionally,all diagnostic characteristics may correlate with immune cells to varying degrees.Conclusions The candidate hub genes(CD177,CYSTM1,and MMP8)were identified,and the nomogram was constructed for pediatric sepsis diagnosis.Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.
基金approved by the Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,China(No.2022ZSLYEC-227)Participants did not need informed consent to partici-pate in the study before taking part in this retrospective study.
文摘Background:The tumor microenvironment plays an essential role in the therapeutic response to immunotherapy.It is necessary to identify immune cell infiltration(ICI)subtypes for evaluating prognosis and therapeutic benefits.This study aimed to evaluate the ICI score as an effective prognostic biomarker for immune response.Methods:The cell-type identification by estimating relative subsets of RNA transcripts and the estimation of stromal and immune cells in malignant tumors using expression methods were used to analyse ICI landscapes in 161 colorectal cancer(CRC)samples with patients’clinical and prognostic data,RNA sequencing data,and whole-exome sequencing data from the Sixth Affiliated Hospital,Sun Yat-sen University(Guangzhou,China).Statistical analysis and data processing were conducted to calculate ICI scores,and to analyse the prognosis of CRC patients with different ICI scores and other features.A similar analysis with RNA sequencing and clinical data of colon adenocarcinoma(COAD)samples from The Cancer Genome Atlas(TCGA)database was conducted to confirm the correctness of the findings.Results:The high-ICI score group with a better prognosis(hazard ratio[HR],2.19;95%confidence interval[CI],1.03–4.64;logrank test,P=0.036)was characterized by the increased tumor mutational burden and interleukin-17(IL-17)signaling pathway.Significant differences in the prognosis and the expression levels of immune checkpoints and chemokine marker genes were found between the two ICI score groups.For COAD samples from TCGA,the results also showed a significant difference in patients’prognosis between the two ICI score groups(HR,1.72;95%CI,1.00–2.96;log-rank test,P=0.047).Conclusions:Tumor heterogeneity induced differences in identifying ICI subtypes of CRC patients.The ICI score may serve as an effective biomarker for predicting prognosis,help identify new therapeutic markers for CRC,and develop novel effective immune checkpoint blockade therapies.
