Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq dat...Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.展开更多
In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarc...In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such tumors.Early detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor prognosis.Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor prognosis.SBAs are linked to genetic disorders and risk factors,including chronic inflammatory conditions.The unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis.Programmed cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic value.Microsatellite instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to immunotherapy.The presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI tumors.Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.展开更多
Background:Cholangiocarcinoma(CCA)is highly malignant and has a poor prognosis has a high malignant degree and poor prognosis.The purpose of this study is to develop a new prognostic model based on genes related to th...Background:Cholangiocarcinoma(CCA)is highly malignant and has a poor prognosis has a high malignant degree and poor prognosis.The purpose of this study is to develop a new prognostic model based on genes related to the tumor microenvironment(TME).Methods:Derived from the discerned differentially expressed genes within The Cancer Genome Atlas(TCGA)dataset,this investigation employed the methodology of weighted gene co-expression network analysis(WGCNA)to ascertain gene co-expressed modules intricately linked to the Tumor Microenvironment(TME)among Cholangiocarcinoma(CCA)patients.The genes associated with prognosis,as identified through Cox regression analysis,were employed in the formulation of a predictive model.This model underwent validation,leading to the development of a risk score formula and nomogram.Concurrently,we validated the model’s reliability using data from CCA patients in the Gene Expression Omnibus(GEO)database(accession:GSE107943).Results:6139 DEGs were divided into 10 co-expressed gene modules using WGCNA.Among these,two modules(blue module with 832 genes and brown module with 1379 genes)showed high correlation with the TME.Five prognostic genes(BNIP3,COL4A3,SPRED3,CEBPB,PLOD2)were identified through Cox regression analysis,and a prognostic model and risk score formula were developed based on these genes.Risk score formula:Risk score=BNIP3×1.70520-COL4A3×2.39815+SPRED3×1.17936+CEBPB×0.40456+PLOD2×0.24785.Kaplan-Meier survival analysis revealed that the survival probabilities of the low-risk group were significantly higher than those of the high-risk group.Furthermore,the related evaluation indexes suggested that the model exhibited strong predictive ability.Conclusion:The prognostic model,based on five TME-related genes(BNIP3,COL4A3,SPRED3,CEBPB,PLOD2),could accurately assess the prognosis of CCA patients to aid in guiding clinical decisions.展开更多
Cancer,a disease as intricate as it is devastating,continues to challenge the medical and scientific community[1].Its complex nature is epitomized by the tumor microenvironment and tumor heterogeneity.As we delve deep...Cancer,a disease as intricate as it is devastating,continues to challenge the medical and scientific community[1].Its complex nature is epitomized by the tumor microenvironment and tumor heterogeneity.As we delve deeper into the realms of cancer research,the advent of transcriptome analysis has emerged as a powerful torchbearer,illuminating our understanding of these enigmatic facets of cancer biology[2].展开更多
BACKGROUND Comprehensive genomic analysis has shown that small bowel adenocarcinoma(SBA)has different genomic profiles from gastric and colorectal cancers.Hence,it is essential to establish chemotherapeutic regimens b...BACKGROUND Comprehensive genomic analysis has shown that small bowel adenocarcinoma(SBA)has different genomic profiles from gastric and colorectal cancers.Hence,it is essential to establish chemotherapeutic regimens based on SBA characteristics.The expression of programmed cell death-ligand 1(PD-L1)and programmed cell death-ligand 2(PD-L2)in SBA is not fully understood.Anti-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes(TILs);therefore,the status of TILs in the tumor microenvironment(TME)may influence their efficacy.The ratio of FoxP3+to CD8+T cells has been reported to be useful in predicting the prognosis of digestive system cancers.AIM To investigate the clinicopathological significance of PD-L1/2 expression according to the status of TILs in SBA tissues.METHODS We performed immunohistochemical analysis for PD-L1,PD-L2,CD8,FoxP3,and DNA mismatch repair(MMR)proteins using formalin-fixed,paraffin-embedded tissues from 50 patients diagnosed with primary SBA.The immunoreactivities of PD-L1 and PD-L2 were determined separately in tumor cells and tumor-infiltrating immune cells throughout the tumor center and invasive margins,and finally evaluated using the combined positive score(CPS).We assessed CD8+and FoxP3+T cells in the intratumoral and tumor-surrounding stroma.Subsequently,we calculated and summed the ratio of FoxP3 to CD8+T cell counts.Immune-related cell densities were graded as low or high.Immunohistochemical results were compared with clinicopathological factors and patient prognosis.The distribution of cancer-specific survival(CSS)was estimated using the Kaplan–Meier method,and the log-rank test was used to test for significant differences in CSS.A Cox proportional hazard model was also used to assess the effect of tumor variables on CSS.RESULTS PD-L1 expression was positive in 34%in tumor cells(T-PD-L1)and 54%in tumor-infiltrating immune cells(I-PDL1)of the cases examined.T-PD-L2 was positive in 34%and I-PD-L2 was positive in 42%of the cases.PD-L1 CPS≥10 and PD-L2 CPS≥10 were observed in 50%and 56%of the cases,respectively.Deficient MMR(dMMR)was 14%of the cases.T-PD-L1,I-PD-L1 and PD-L1 CPS≥10 were all significantly associated with dMMR(P=0.037,P=0.009,and P=0.005,respectively).T-PD-L1,I-PD-L1,and PD-L1 CPS≥10 were all associated with deeper depth of invasion(P=0.001,P=0.024,and P=0.002,respectively).I-PD-L2 expression and PD-L2 CPS≥10 were significantly higher in the differentiated histological type(P=0.015 and P=0.030,respectively).The I-PD-L1 and IPD-L2 levels were significantly associated with better CSS(P=0.037 and P=0.015,respectively).CD8-high was significantly associated with less lymph node metastasis(P=0.047),less distant metastasis(P=0.024),less peritoneal dissemination(P=0.034),and earlier TNM stage(P=0.047).The CD8-high group had better prognosis than the CD8-low group(P=0.018).FoxP3 expression was not associated with any clinicopathological factors or prognosis.We found that patients with PD-L2 CPS≥10 tended to have worse prognosis in the FoxP3/CD8-low group(P=0.088).CONCLUSION The clinicopathological significance of PD-L1/2 expression may differ depending on the TME status.Immune checkpoint inhibitors may improve the prognosis of SBA patients with low FoxP3/CD8 ratio and PD-L2 expression.展开更多
Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has...Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic activities.This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)technologies.Here,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity.Furthermore,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor progression.Mechanistically,CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways.We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes.Furthermore,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted mice.Taken together,we provide new insights into the anti-tumor effects of CBD.展开更多
Tumor microenvironment(TME)with the particular features of severe hypoxia,insufficient endogenous H2O2,and overexpression of glutathione(GSH)markedly reduced the antitumor efficacy of monotherapy.Herein,a TME-responsi...Tumor microenvironment(TME)with the particular features of severe hypoxia,insufficient endogenous H2O2,and overexpression of glutathione(GSH)markedly reduced the antitumor efficacy of monotherapy.Herein,a TME-responsive multifunctional nanoplatform(Bi2S3@Bi@PDA-HA/Art NRs)was presented for synergistic photothermal therapy(PTT),chemodynamic therapy(CDT),and photodynamic therapy(PDT)to achieve better therapeutic outcomes.The Z-scheme heterostructured bismuth sulfide@bismuth nanorods(Bi2S3@Bi NRs)guaranteed excellent photothermal performance of the nanoplatform.Moreover,its ability to produce O2 and reactive oxygen species(ROS)synchronously could relieve tumor hypoxia and improve PDT outcomes.The densely coated polydopamine/ammonium bicarbonate(PDA/ABC)and hyaluronic acid(HA)layers on the surface of the nanoplatform enhanced the cancer-targeting capacity and induced the acidic TME-triggered in situ“bomb-like”release of Art.The CDT treatment was achieved by activating the released Art through intracellular Fe2+ions in an H2O2-independent manner.Furthermore,decreasing the glutathione peroxidase 4(GPX4)levels by Art could also increase the PDT efficiency of Bi2S3@Bi NRs.Owing to the synergistic effect,this nanoplatform displayed improved antitumor efficacy with minimal toxicity both in vitro and in vivo.Our design sheds light on the application of phototherapy combined with the traditional Chinese medicine monomer-artesunate in treating the hypoxic tumor.展开更多
BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to ...BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to the regulation of the TME.AIM To determine the role of CD93 in GC.METHODS Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas.Additionally,RNA-seq data sets from Gene Expression Omnibus(GSE118916,GSE52138,GSE79973,GSE19826,and GSE84433)were applied to validate the results.We performed the immune infiltration analyses using ESTIMATE,CIBERSORT,and ssGSEA.Furthermore,weighted gene co-expression network analysis(WGCNA)was conducted to identify the immunerelated genes.RESULTS Compared to normal tissues,CD93 significantly enriched in tumor tissues(t=4.669,95%CI:0.342-0.863,P<0.001).Higher expression of CD93 was significantly associated with shorter overall survival(hazard ratio=1.62,95%CI:1.09-2.4,P=0.017),less proportion of CD8 T and activated natural killer cells in the TME(P<0.05),and lower tumor mutation burden(t=4.131,95%CI:0.721-0.256,P<0.001).Genes co-expressed with CD93 were mainly enriched in angiogenesis.Moreover,11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA.CONCLUSION CD93 is a novel prognostic and diagnostic biomarker for GC,that is closely related to the immune infiltration in the TME.Although this retrospective study was a comprehensive analysis,the prospective cohort studies are preferred to further confirm these conclusions.展开更多
Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activiti...Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities.Olfactory receptor family 7 subfamily E member 47 pseudogene(OR7E47P)is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment(TME)of lung adenocarcinoma(LUAD).This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma(LUSC).Methods Clinical and molecular information from The Cancer Genome Atlas(TCGA)LUSC cohort was used to identify OR7E47P-related immune genes(ORIGs)by weighted gene correlation network analysis(WGCNA).Based on the ORIGs,2 OR7E47P clusters were identified using non-negative matrix factorization(NMF)clustering,and the stability of the clustering was tested by an extreme gradient boosting classifier(XGBoost).LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model(ORPScore)for immunotherapy.The Botling cohorts and 8 immunotherapy cohorts(the Samstein,Braun,Jung,Gide,IMvigor210,Lauss,Van Allen,and Cho cohorts)were included as independent validation cohorts.Results OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC.A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters(Cluster 1 and Cluster 2)with distinct immune,mutation,and stromal programs.Compared to Cluster 1,Cluster 2 had more infiltration by immune and stromal cells,lower mutation rates of driver genes,and higher expression of immune-related proteins.The clustering performed well in the internal and 5 external validation cohorts.Based on the 7 ORIGs(HOPX,STX2,WFS,DUSP22,SLFN13,GGCT,and CCSER2),the ORPScore was constructed to predict the prognosis and the treatment response.In addition,the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients.The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts.Conclusion Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC.ORIGs can be applied to molecularly stratify patients,and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.展开更多
Colorectal cancer(CRC)remains the third most prevalent cancer disease and involves a multi-step process in which intestinal cells acquire malignant characteristics.It is well established that the appearance of distal ...Colorectal cancer(CRC)remains the third most prevalent cancer disease and involves a multi-step process in which intestinal cells acquire malignant characteristics.It is well established that the appearance of distal metastasis in CRC patients is the cause of a poor prognosis and treatment failure.Nevertheless,in the last decades,CRC aggressiveness and progression have been attributed to a specific cell population called CRC stem cells(CCSC)with features like tumor initiation capacity,self-renewal capacity,and acquired multidrug resistance.Emerging data highlight the concept of this cell subtype as a plastic entity that has a dynamic status and can be originated from different types of cells through genetic and epigenetic changes.These alterations are modulated by complex and dynamic crosstalk with environmental factors by paracrine signaling.It is known that in the tumor niche,different cell types,structures,and biomolecules coexist and interact with cancer cells favoring cancer growth and development.Together,these components constitute the tumor microenvironment(TME).Most recently,researchers have also deepened the influence of the complex variety of microorganisms that inhabit the intestinal mucosa,collectively known as gut microbiota,on CRC.Both TME and microorganisms participate in inflammatory processes that can drive the initiation and evolution of CRC.Since in the last decade,crucial advances have been made concerning to the synergistic interaction among the TME and gut microorganisms that condition the identity of CCSC,the data exposed in this review could provide valuable insights into the biology of CRC and the development of new targeted therapies.展开更多
Spatial omics technology integrates the concept of space into omics research and retains the spatial information of tissues or organs while obtaining molecular information.It is characterized by the ability to visuali...Spatial omics technology integrates the concept of space into omics research and retains the spatial information of tissues or organs while obtaining molecular information.It is characterized by the ability to visualize changes in molecular information and yields intuitive and vivid visual results.Spatial omics technologies include spatial transcriptomics,spatial proteomics,spatial metabolomics,and other technologies,the most widely used of which are spatial transcriptomics and spatial proteomics.The tumor microenvironment refers to the surrounding microenvironment in which tumor cells exist,including the surrounding blood vessels,immune cells,fibroblasts,bone marrow-derived inflammatory cells,various signaling molecules,and extracellular matrix.A key issue in modern tumor biology is the application of spatial omics to the study of the tumor microenvironment,which can reveal problems that conventional research techniques cannot,potentially leading to the development of novel therapeutic agents for cancer.This paper summarizes the progress of research on spatial transcriptomics and spatial proteomics technologies for characterizing the tumor immune microenvironment.展开更多
Tumor proliferation,metabolism,metastasis,and chemoresistance are intimately related to the tumor microenvironment(TME).The metabolic reprogramming of tumor cells is a hallmark of their adaptation to hypoxic and nutri...Tumor proliferation,metabolism,metastasis,and chemoresistance are intimately related to the tumor microenvironment(TME).The metabolic reprogramming of tumor cells is a hallmark of their adaptation to hypoxic and nutrient-deficient TMEs.Exosomes,a type of extracellular vesicle,have been found to regulate the crosstalk between tumor cells and the TME,affecting tumor metabolic reprogramming.In this review,we introduce the metabolic characteristics of tumor cells;describe the crosstalk between tumor cells and the TME in terms of glucose metabolism,lipid metabolism,and amino acid metabolism through exosomes;and provide an overview of the diagnostic and therapeutic potential of exosomes.A better understanding of tumor metabolism would provide a broader perspective about the mechanisms underlying tumor pathology and would facilitate the search for therapeutic targets and guide more individualized tumor treatment.展开更多
The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma(OS).However,the landscape and dynamics of immune cells in OS are poorly characterized.By analyzing single-ce...The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma(OS).However,the landscape and dynamics of immune cells in OS are poorly characterized.By analyzing single-cell RNA sequencing(sc RNA-seq)data,which characterize the transcription state at single-cell resolution,we produced an atlas of the immune microenvironment in OS.The results suggested that a cluster of regulatory dendritic cells(DCs)might shape the immunosuppressive microenvironment in OS by recruiting regulatory T cells.We also found that major histocompatibility complex class I(MHC-I)molecules were downregulated in cancer cells.The findings indicated a reduction in tumor immunogenicity in OS,which can be a potential mechanism of tumor immune escape.Of note,CD24 was identified as a novel“don’t eat me”signal that contributed to the immune evasion of OS cells.Altogether,our findings provide insights into the immune landscape of OS,suggesting that myeloid-targeted immunotherapy could be a promising approach to treat OS.展开更多
Mechanical forces in the tumor microenvironment(TME)are associated with tumor growth,proliferation,and drug resistance.Strong mechanical forces in tumors alter the metabolism and behavior of cancer cells,thus promotin...Mechanical forces in the tumor microenvironment(TME)are associated with tumor growth,proliferation,and drug resistance.Strong mechanical forces in tumors alter the metabolism and behavior of cancer cells,thus promoting tumor progression and metastasis.Mechanical signals are transformed into biochemical signals,which activate tumorigenic signaling pathways through mechanical transduction.Cancer immunotherapy has recently made exciting progress,ushering in a new era of“chemo-free”treatments.However,immunotherapy has not achieved satisfactory results in a variety of tumors,because of the complex tumor microenvironment.Herein,we discuss the effects of mechanical forces on the tumor immune microenvironment and highlight emerging therapeutic strategies for targeting mechanical forces in immunotherapy.展开更多
Glioblastoma(GBM)is a malignant adult brain tumor for which 90%of patients experience recurrence within a year after surgery1.Evolution confers treatment resistance capabilities on tumors2.The diversification of malig...Glioblastoma(GBM)is a malignant adult brain tumor for which 90%of patients experience recurrence within a year after surgery1.Evolution confers treatment resistance capabilities on tumors2.The diversification of malignant and non-malignant(i.e.,stromal and immune cell)compartments in the tumor microenvironment(TME)during tumor evolution3-7 eventually results in the formation of a complex interaction network that promotes tumor progression.展开更多
Multiple endocrine neoplasia 1(MEN1)syndrome,a disease arising from a genetic predisposition to tumor development caused by MEN1 loss-of-function mutations,is characterized by the combined occurrence of neuroendocrine...Multiple endocrine neoplasia 1(MEN1)syndrome,a disease arising from a genetic predisposition to tumor development caused by MEN1 loss-of-function mutations,is characterized by the combined occurrence of neuroendocrine tumors in multiple human organs.With advances in diagnostic technologies and improvements in living standards.展开更多
The tumor microenvironment(TME)plays a crucial role in facilitating tumorigenesis and progression.Consequently,there is significant research interest within the oncology community in developing interventions that targ...The tumor microenvironment(TME)plays a crucial role in facilitating tumorigenesis and progression.Consequently,there is significant research interest within the oncology community in developing interventions that target the TME.Extensive research has been conducted on the mechanism of traditional Chinese medicine(TCM)in tumor therapy,revealing notable similarities between its theoretical framework and that of the TME.TCM has the ability to regulate various components of the microenvironment,including the modulation of proportions of T cell subsets,enhancement of the quantity and activity of NK cells,regulation of polarization of tumor-associated macrophages,suppression of expression of myeloid-derived suppressor cells,reduction of accumulation of tumor-associated endothelial cells,downregulation of the quantity and function of tumor-associated fibroblasts,and modulation of the architecture of the extracellular matrix.These multifaceted interventions ultimately lead to the attainment of anti-tumor objectives.This comprehensive review encompasses a thorough analysis of relevant literature from both domestic and international sources,with a specific emphasis on elucidating the mechanisms through which TCM compound formulas,single drugs,and monomeric components regulate the TME.展开更多
In the tumor immune microenvironment, CD8<sup>+</sup> T cells differentiate towards functional failure. The exhaustion of CD8<sup>+</sup> T cells (Tex) showed varying degrees of effect dysfunct...In the tumor immune microenvironment, CD8<sup>+</sup> T cells differentiate towards functional failure. The exhaustion of CD8<sup>+</sup> T cells (Tex) showed varying degrees of effect dysfunction, loss of proliferation ability, and sustained high expression of a variety of inhibitory receptors, with metabolic and epigenetic changes. Tex cells are heterogeneous, including several subsets with different characteristics at different stages of differentiation. Immune checkpoint inhibitors (ICIs) can restore the effect or function of Tex cells, indicating that this T cell subset plays a key role in tumor immunotherapy. The understanding of the mechanism of CD8<sup>+</sup> T cell exhaustion will be helpful to the implementation of tumor immunotherapy. This article reviews the production, differentiation and functional characteristics of Tex cells and their relationship with tumor immunotherapy.展开更多
Breast cancer has been shown to live in the tumor microenvironment, which consists of not only breast cancer cells themselves but also a significant amount of pathophysiologically altered surrounding stroma and cells....Breast cancer has been shown to live in the tumor microenvironment, which consists of not only breast cancer cells themselves but also a significant amount of pathophysiologically altered surrounding stroma and cells. Diverse components of the breast cancer microenvironment, such as suppressive immune cells, re-programmed fibroblast cells, altered extracellular matrix(ECM) and certain soluble factors, synergistically impede an effective anti-tumor response and promote breast cancer progression and metastasis. Among these components, stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways,whereas the ECM features biochemical and biomechanical changes. However, triple-negative breast cancer(TNBC), the most aggressive subtype of this disease that lacks effective therapies available for other subtypes, is considered to feature a unique microenvironment distinct from that of other subtypes, especially compared to Luminal A subtype. Because these changes are now considered to significantly impact breast cancer development and progression, these unique alterations may serve as promising prognostic factors of clinical outcome or potential therapeutic targets for the treatment of TNBC. In this review, we focus on the composition of the TNBC microenvironment, concomitant distinct biological alteration, specific interplay between various cell types and TNBC cells, and the prognostic implications of these findings.展开更多
基金Liuzhou City's Top Ten Hundred Talents Project,Liuzhou Science and Technology Project(Grant Nos.2021CBC0126 and 2021CBC0123)Guangxi Zhuang Autonomous Region Health and Family Planning Commission Projects(Z20210561,Z20210903)+1 种基金liuzhou Scienceand Technology Plan Projects(2021CBC0121,2021CBC0128).
文摘Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.
文摘In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such tumors.Early detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor prognosis.Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor prognosis.SBAs are linked to genetic disorders and risk factors,including chronic inflammatory conditions.The unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis.Programmed cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic value.Microsatellite instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to immunotherapy.The presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI tumors.Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.
基金supported by Medical Scientific Research Foundation of Chongqing of China(2022MSXM048).
文摘Background:Cholangiocarcinoma(CCA)is highly malignant and has a poor prognosis has a high malignant degree and poor prognosis.The purpose of this study is to develop a new prognostic model based on genes related to the tumor microenvironment(TME).Methods:Derived from the discerned differentially expressed genes within The Cancer Genome Atlas(TCGA)dataset,this investigation employed the methodology of weighted gene co-expression network analysis(WGCNA)to ascertain gene co-expressed modules intricately linked to the Tumor Microenvironment(TME)among Cholangiocarcinoma(CCA)patients.The genes associated with prognosis,as identified through Cox regression analysis,were employed in the formulation of a predictive model.This model underwent validation,leading to the development of a risk score formula and nomogram.Concurrently,we validated the model’s reliability using data from CCA patients in the Gene Expression Omnibus(GEO)database(accession:GSE107943).Results:6139 DEGs were divided into 10 co-expressed gene modules using WGCNA.Among these,two modules(blue module with 832 genes and brown module with 1379 genes)showed high correlation with the TME.Five prognostic genes(BNIP3,COL4A3,SPRED3,CEBPB,PLOD2)were identified through Cox regression analysis,and a prognostic model and risk score formula were developed based on these genes.Risk score formula:Risk score=BNIP3×1.70520-COL4A3×2.39815+SPRED3×1.17936+CEBPB×0.40456+PLOD2×0.24785.Kaplan-Meier survival analysis revealed that the survival probabilities of the low-risk group were significantly higher than those of the high-risk group.Furthermore,the related evaluation indexes suggested that the model exhibited strong predictive ability.Conclusion:The prognostic model,based on five TME-related genes(BNIP3,COL4A3,SPRED3,CEBPB,PLOD2),could accurately assess the prognosis of CCA patients to aid in guiding clinical decisions.
基金National Nature Science Foundation for young scientist in Jiangsu Province(BK20220729).
文摘Cancer,a disease as intricate as it is devastating,continues to challenge the medical and scientific community[1].Its complex nature is epitomized by the tumor microenvironment and tumor heterogeneity.As we delve deeper into the realms of cancer research,the advent of transcriptome analysis has emerged as a powerful torchbearer,illuminating our understanding of these enigmatic facets of cancer biology[2].
基金The study was reviewed and approved by the Nippon Medical School Institutional Review Board(Approval No.B-2020-164).
文摘BACKGROUND Comprehensive genomic analysis has shown that small bowel adenocarcinoma(SBA)has different genomic profiles from gastric and colorectal cancers.Hence,it is essential to establish chemotherapeutic regimens based on SBA characteristics.The expression of programmed cell death-ligand 1(PD-L1)and programmed cell death-ligand 2(PD-L2)in SBA is not fully understood.Anti-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes(TILs);therefore,the status of TILs in the tumor microenvironment(TME)may influence their efficacy.The ratio of FoxP3+to CD8+T cells has been reported to be useful in predicting the prognosis of digestive system cancers.AIM To investigate the clinicopathological significance of PD-L1/2 expression according to the status of TILs in SBA tissues.METHODS We performed immunohistochemical analysis for PD-L1,PD-L2,CD8,FoxP3,and DNA mismatch repair(MMR)proteins using formalin-fixed,paraffin-embedded tissues from 50 patients diagnosed with primary SBA.The immunoreactivities of PD-L1 and PD-L2 were determined separately in tumor cells and tumor-infiltrating immune cells throughout the tumor center and invasive margins,and finally evaluated using the combined positive score(CPS).We assessed CD8+and FoxP3+T cells in the intratumoral and tumor-surrounding stroma.Subsequently,we calculated and summed the ratio of FoxP3 to CD8+T cell counts.Immune-related cell densities were graded as low or high.Immunohistochemical results were compared with clinicopathological factors and patient prognosis.The distribution of cancer-specific survival(CSS)was estimated using the Kaplan–Meier method,and the log-rank test was used to test for significant differences in CSS.A Cox proportional hazard model was also used to assess the effect of tumor variables on CSS.RESULTS PD-L1 expression was positive in 34%in tumor cells(T-PD-L1)and 54%in tumor-infiltrating immune cells(I-PDL1)of the cases examined.T-PD-L2 was positive in 34%and I-PD-L2 was positive in 42%of the cases.PD-L1 CPS≥10 and PD-L2 CPS≥10 were observed in 50%and 56%of the cases,respectively.Deficient MMR(dMMR)was 14%of the cases.T-PD-L1,I-PD-L1 and PD-L1 CPS≥10 were all significantly associated with dMMR(P=0.037,P=0.009,and P=0.005,respectively).T-PD-L1,I-PD-L1,and PD-L1 CPS≥10 were all associated with deeper depth of invasion(P=0.001,P=0.024,and P=0.002,respectively).I-PD-L2 expression and PD-L2 CPS≥10 were significantly higher in the differentiated histological type(P=0.015 and P=0.030,respectively).The I-PD-L1 and IPD-L2 levels were significantly associated with better CSS(P=0.037 and P=0.015,respectively).CD8-high was significantly associated with less lymph node metastasis(P=0.047),less distant metastasis(P=0.024),less peritoneal dissemination(P=0.034),and earlier TNM stage(P=0.047).The CD8-high group had better prognosis than the CD8-low group(P=0.018).FoxP3 expression was not associated with any clinicopathological factors or prognosis.We found that patients with PD-L2 CPS≥10 tended to have worse prognosis in the FoxP3/CD8-low group(P=0.088).CONCLUSION The clinicopathological significance of PD-L1/2 expression may differ depending on the TME status.Immune checkpoint inhibitors may improve the prognosis of SBA patients with low FoxP3/CD8 ratio and PD-L2 expression.
基金supported by the National Key Research and Development Plan,China(Grant No.:2022YFC3500202)the Natural Science Foundation of China(Grant Nos.:82172558,and 82205024)+4 种基金the Scientific and Technological Innovation Action Plan of Natural Science Foundation Project of Shanghai,China(Grant No.:22ZR1447400)the Scientific and Technological Innovation Action Plan,China(Grant No.:22ZR1447400)the Fundamental Research Funds for the Central Universities,China(Grant Nos.:020814380179,020814380174)the Distinguished Young Scholars of Nanjing,China(Grant No.:JQX20008)the School of Life Science(NJU)-Sipimo Joint Funds and Mountain Climbing Talents Project of Nanjing University,China(Grant No.:2015018).
文摘Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic activities.This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)technologies.Here,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity.Furthermore,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor progression.Mechanistically,CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways.We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes.Furthermore,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted mice.Taken together,we provide new insights into the anti-tumor effects of CBD.
基金Financial support was provided by the National Natural Science Foundation of China(grant no.21807024)the Youth Top-notch Talents Supporting Plan of Hebei Province(QNBJ19004)+4 种基金Scientific Research Foundation of Hebei Province for the Returned Overseas Chinese Scholars(C20220508)the Science and Technology Project of Hebei Education Department(no.ZD2021072)the Central Guidance on Local Science and Technology Development Fund of Hebei Province(226Z2601G)Science Fun for Creative Research Groups of Natural Science Foundation of Hebei Province(no.H2020206474)supported by the Postdoctoral Fund of Hebei Medical University.
文摘Tumor microenvironment(TME)with the particular features of severe hypoxia,insufficient endogenous H2O2,and overexpression of glutathione(GSH)markedly reduced the antitumor efficacy of monotherapy.Herein,a TME-responsive multifunctional nanoplatform(Bi2S3@Bi@PDA-HA/Art NRs)was presented for synergistic photothermal therapy(PTT),chemodynamic therapy(CDT),and photodynamic therapy(PDT)to achieve better therapeutic outcomes.The Z-scheme heterostructured bismuth sulfide@bismuth nanorods(Bi2S3@Bi NRs)guaranteed excellent photothermal performance of the nanoplatform.Moreover,its ability to produce O2 and reactive oxygen species(ROS)synchronously could relieve tumor hypoxia and improve PDT outcomes.The densely coated polydopamine/ammonium bicarbonate(PDA/ABC)and hyaluronic acid(HA)layers on the surface of the nanoplatform enhanced the cancer-targeting capacity and induced the acidic TME-triggered in situ“bomb-like”release of Art.The CDT treatment was achieved by activating the released Art through intracellular Fe2+ions in an H2O2-independent manner.Furthermore,decreasing the glutathione peroxidase 4(GPX4)levels by Art could also increase the PDT efficiency of Bi2S3@Bi NRs.Owing to the synergistic effect,this nanoplatform displayed improved antitumor efficacy with minimal toxicity both in vitro and in vivo.Our design sheds light on the application of phototherapy combined with the traditional Chinese medicine monomer-artesunate in treating the hypoxic tumor.
文摘BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to the regulation of the TME.AIM To determine the role of CD93 in GC.METHODS Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas.Additionally,RNA-seq data sets from Gene Expression Omnibus(GSE118916,GSE52138,GSE79973,GSE19826,and GSE84433)were applied to validate the results.We performed the immune infiltration analyses using ESTIMATE,CIBERSORT,and ssGSEA.Furthermore,weighted gene co-expression network analysis(WGCNA)was conducted to identify the immunerelated genes.RESULTS Compared to normal tissues,CD93 significantly enriched in tumor tissues(t=4.669,95%CI:0.342-0.863,P<0.001).Higher expression of CD93 was significantly associated with shorter overall survival(hazard ratio=1.62,95%CI:1.09-2.4,P=0.017),less proportion of CD8 T and activated natural killer cells in the TME(P<0.05),and lower tumor mutation burden(t=4.131,95%CI:0.721-0.256,P<0.001).Genes co-expressed with CD93 were mainly enriched in angiogenesis.Moreover,11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA.CONCLUSION CD93 is a novel prognostic and diagnostic biomarker for GC,that is closely related to the immune infiltration in the TME.Although this retrospective study was a comprehensive analysis,the prospective cohort studies are preferred to further confirm these conclusions.
基金the Wuhan University Medical Faculty Innovation Seed Fund Cultivation Project(No.TFZZ2018025)the Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province(No.CXPJJH12000001-2020313)the National Natural Science Foundation of China(No.81670123 and No.81670144).
文摘Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities.Olfactory receptor family 7 subfamily E member 47 pseudogene(OR7E47P)is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment(TME)of lung adenocarcinoma(LUAD).This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma(LUSC).Methods Clinical and molecular information from The Cancer Genome Atlas(TCGA)LUSC cohort was used to identify OR7E47P-related immune genes(ORIGs)by weighted gene correlation network analysis(WGCNA).Based on the ORIGs,2 OR7E47P clusters were identified using non-negative matrix factorization(NMF)clustering,and the stability of the clustering was tested by an extreme gradient boosting classifier(XGBoost).LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model(ORPScore)for immunotherapy.The Botling cohorts and 8 immunotherapy cohorts(the Samstein,Braun,Jung,Gide,IMvigor210,Lauss,Van Allen,and Cho cohorts)were included as independent validation cohorts.Results OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC.A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters(Cluster 1 and Cluster 2)with distinct immune,mutation,and stromal programs.Compared to Cluster 1,Cluster 2 had more infiltration by immune and stromal cells,lower mutation rates of driver genes,and higher expression of immune-related proteins.The clustering performed well in the internal and 5 external validation cohorts.Based on the 7 ORIGs(HOPX,STX2,WFS,DUSP22,SLFN13,GGCT,and CCSER2),the ORPScore was constructed to predict the prognosis and the treatment response.In addition,the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients.The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts.Conclusion Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC.ORIGs can be applied to molecularly stratify patients,and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.
基金Supported by Agencia Nacional de Promoción Científica y Tecnológica,No.PICT-2020-SERIEA-03440 and PICT-2013-1441Consejo Nacional de Investigaciones Científicas y Técnicas,No.PIP11220200103061CO and PIP11220150100350CO+3 种基金Instituto Nacional del Cáncer Asistencia Financiera Ⅱ,RESOL 493/14,No.2002-4395-14-1Instituto Nacional del Cáncer Asistencia Financiera Ⅲ-2016-2017,RESOL-2016-1006-E-APN-MS,No.2002-3862-16-1 CANCERUniversidad Nacional del Sur,No.PGI:24/B230 and PGI:24/B303Fundación Alberto J Roemmers of Argentina.
文摘Colorectal cancer(CRC)remains the third most prevalent cancer disease and involves a multi-step process in which intestinal cells acquire malignant characteristics.It is well established that the appearance of distal metastasis in CRC patients is the cause of a poor prognosis and treatment failure.Nevertheless,in the last decades,CRC aggressiveness and progression have been attributed to a specific cell population called CRC stem cells(CCSC)with features like tumor initiation capacity,self-renewal capacity,and acquired multidrug resistance.Emerging data highlight the concept of this cell subtype as a plastic entity that has a dynamic status and can be originated from different types of cells through genetic and epigenetic changes.These alterations are modulated by complex and dynamic crosstalk with environmental factors by paracrine signaling.It is known that in the tumor niche,different cell types,structures,and biomolecules coexist and interact with cancer cells favoring cancer growth and development.Together,these components constitute the tumor microenvironment(TME).Most recently,researchers have also deepened the influence of the complex variety of microorganisms that inhabit the intestinal mucosa,collectively known as gut microbiota,on CRC.Both TME and microorganisms participate in inflammatory processes that can drive the initiation and evolution of CRC.Since in the last decade,crucial advances have been made concerning to the synergistic interaction among the TME and gut microorganisms that condition the identity of CCSC,the data exposed in this review could provide valuable insights into the biology of CRC and the development of new targeted therapies.
基金supported by Basic and Applied Basic Research Foundation of Guangdong Province(No.2022A1111220217)Medical Scientific Research Foundation of Guangdong Province(Nos.A2023216,A2022124)+3 种基金Science and Technology Program of Guangzhou(Nos.202201010840,202201010810,202102080132,202002030032,202002020023)Health Commission Program of Guangzhou(20212A010021,20201A010081,20211A011116)Science and Technology Project of Panyu,Guangzhou(2022-Z04-009,2022-Z04-090,2022-Z04-072,2021-Z04-013,2020-Z04-026,2019-Z04-02)Scientific Research Project of Guangzhou Panyu Central Hospital(Nos.2022Y002,2021Y004,2021Y002).
文摘Spatial omics technology integrates the concept of space into omics research and retains the spatial information of tissues or organs while obtaining molecular information.It is characterized by the ability to visualize changes in molecular information and yields intuitive and vivid visual results.Spatial omics technologies include spatial transcriptomics,spatial proteomics,spatial metabolomics,and other technologies,the most widely used of which are spatial transcriptomics and spatial proteomics.The tumor microenvironment refers to the surrounding microenvironment in which tumor cells exist,including the surrounding blood vessels,immune cells,fibroblasts,bone marrow-derived inflammatory cells,various signaling molecules,and extracellular matrix.A key issue in modern tumor biology is the application of spatial omics to the study of the tumor microenvironment,which can reveal problems that conventional research techniques cannot,potentially leading to the development of novel therapeutic agents for cancer.This paper summarizes the progress of research on spatial transcriptomics and spatial proteomics technologies for characterizing the tumor immune microenvironment.
基金This work was supported by grants from the National Natural Science Foundation of China(No.82173125 and 81974374).
文摘Tumor proliferation,metabolism,metastasis,and chemoresistance are intimately related to the tumor microenvironment(TME).The metabolic reprogramming of tumor cells is a hallmark of their adaptation to hypoxic and nutrient-deficient TMEs.Exosomes,a type of extracellular vesicle,have been found to regulate the crosstalk between tumor cells and the TME,affecting tumor metabolic reprogramming.In this review,we introduce the metabolic characteristics of tumor cells;describe the crosstalk between tumor cells and the TME in terms of glucose metabolism,lipid metabolism,and amino acid metabolism through exosomes;and provide an overview of the diagnostic and therapeutic potential of exosomes.A better understanding of tumor metabolism would provide a broader perspective about the mechanisms underlying tumor pathology and would facilitate the search for therapeutic targets and guide more individualized tumor treatment.
基金National Natural Sciences Foundation of China(grant91949203,grant 82072979 and grant 81673456)Nonprofit Central ResearchInstitute Fund of the Chinese Academy of Medical Sciences(2019PT320001)Natural Sciences Foundation of Hubei Province(2020CFB778)。
文摘The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma(OS).However,the landscape and dynamics of immune cells in OS are poorly characterized.By analyzing single-cell RNA sequencing(sc RNA-seq)data,which characterize the transcription state at single-cell resolution,we produced an atlas of the immune microenvironment in OS.The results suggested that a cluster of regulatory dendritic cells(DCs)might shape the immunosuppressive microenvironment in OS by recruiting regulatory T cells.We also found that major histocompatibility complex class I(MHC-I)molecules were downregulated in cancer cells.The findings indicated a reduction in tumor immunogenicity in OS,which can be a potential mechanism of tumor immune escape.Of note,CD24 was identified as a novel“don’t eat me”signal that contributed to the immune evasion of OS cells.Altogether,our findings provide insights into the immune landscape of OS,suggesting that myeloid-targeted immunotherapy could be a promising approach to treat OS.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.81972455 and 81902358)。
文摘Mechanical forces in the tumor microenvironment(TME)are associated with tumor growth,proliferation,and drug resistance.Strong mechanical forces in tumors alter the metabolism and behavior of cancer cells,thus promoting tumor progression and metastasis.Mechanical signals are transformed into biochemical signals,which activate tumorigenic signaling pathways through mechanical transduction.Cancer immunotherapy has recently made exciting progress,ushering in a new era of“chemo-free”treatments.However,immunotherapy has not achieved satisfactory results in a variety of tumors,because of the complex tumor microenvironment.Herein,we discuss the effects of mechanical forces on the tumor immune microenvironment and highlight emerging therapeutic strategies for targeting mechanical forces in immunotherapy.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.91959113,81972358,82261160578,and 82272867)the Beijing Nova Program(Grant No.Z201100006820118)。
文摘Glioblastoma(GBM)is a malignant adult brain tumor for which 90%of patients experience recurrence within a year after surgery1.Evolution confers treatment resistance capabilities on tumors2.The diversification of malignant and non-malignant(i.e.,stromal and immune cell)compartments in the tumor microenvironment(TME)during tumor evolution3-7 eventually results in the formation of a complex interaction network that promotes tumor progression.
基金jointly supported by the National Natural Science Foundation of China(Grant No.U21A20374),National Natural Science Foundation of China(Grant Nos.82141129 and 82141104)Shanghai Municipal Science and Technology Major Project(Grant No.21JC1401500)+4 种基金Scientific Innovation Project of Shanghai Education Committee(Grant No.2019-01-0700-07-E00057)Clinical Research Plan of Shanghai Hospital Development Center(Grant No.SHDC2020CR1006A)Xuhui District Artificial Intelligence Medical Hospital Cooperation Project(Grant No.2021-011)Shanghai Municipal Science and Technology Commission(Grant No.19QA1402100)Shanghai Pujiang Program(Grant No.22PJ1401800).
文摘Multiple endocrine neoplasia 1(MEN1)syndrome,a disease arising from a genetic predisposition to tumor development caused by MEN1 loss-of-function mutations,is characterized by the combined occurrence of neuroendocrine tumors in multiple human organs.With advances in diagnostic technologies and improvements in living standards.
基金supported by the National Natural Science Foundation of China(No.81973771).
文摘The tumor microenvironment(TME)plays a crucial role in facilitating tumorigenesis and progression.Consequently,there is significant research interest within the oncology community in developing interventions that target the TME.Extensive research has been conducted on the mechanism of traditional Chinese medicine(TCM)in tumor therapy,revealing notable similarities between its theoretical framework and that of the TME.TCM has the ability to regulate various components of the microenvironment,including the modulation of proportions of T cell subsets,enhancement of the quantity and activity of NK cells,regulation of polarization of tumor-associated macrophages,suppression of expression of myeloid-derived suppressor cells,reduction of accumulation of tumor-associated endothelial cells,downregulation of the quantity and function of tumor-associated fibroblasts,and modulation of the architecture of the extracellular matrix.These multifaceted interventions ultimately lead to the attainment of anti-tumor objectives.This comprehensive review encompasses a thorough analysis of relevant literature from both domestic and international sources,with a specific emphasis on elucidating the mechanisms through which TCM compound formulas,single drugs,and monomeric components regulate the TME.
文摘In the tumor immune microenvironment, CD8<sup>+</sup> T cells differentiate towards functional failure. The exhaustion of CD8<sup>+</sup> T cells (Tex) showed varying degrees of effect dysfunction, loss of proliferation ability, and sustained high expression of a variety of inhibitory receptors, with metabolic and epigenetic changes. Tex cells are heterogeneous, including several subsets with different characteristics at different stages of differentiation. Immune checkpoint inhibitors (ICIs) can restore the effect or function of Tex cells, indicating that this T cell subset plays a key role in tumor immunotherapy. The understanding of the mechanism of CD8<sup>+</sup> T cell exhaustion will be helpful to the implementation of tumor immunotherapy. This article reviews the production, differentiation and functional characteristics of Tex cells and their relationship with tumor immunotherapy.
文摘Breast cancer has been shown to live in the tumor microenvironment, which consists of not only breast cancer cells themselves but also a significant amount of pathophysiologically altered surrounding stroma and cells. Diverse components of the breast cancer microenvironment, such as suppressive immune cells, re-programmed fibroblast cells, altered extracellular matrix(ECM) and certain soluble factors, synergistically impede an effective anti-tumor response and promote breast cancer progression and metastasis. Among these components, stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways,whereas the ECM features biochemical and biomechanical changes. However, triple-negative breast cancer(TNBC), the most aggressive subtype of this disease that lacks effective therapies available for other subtypes, is considered to feature a unique microenvironment distinct from that of other subtypes, especially compared to Luminal A subtype. Because these changes are now considered to significantly impact breast cancer development and progression, these unique alterations may serve as promising prognostic factors of clinical outcome or potential therapeutic targets for the treatment of TNBC. In this review, we focus on the composition of the TNBC microenvironment, concomitant distinct biological alteration, specific interplay between various cell types and TNBC cells, and the prognostic implications of these findings.
