Purpose: Data on microarray gene expression The Gene Expression Omnibus (GEO) provided information on gene expression. Transcription GEO provided two profiles of human NK cells from breast and adrenal tumors (GSE17950...Purpose: Data on microarray gene expression The Gene Expression Omnibus (GEO) provided information on gene expression. Transcription GEO provided two profiles of human NK cells from breast and adrenal tumors (GSE179509 and GSE143383). Data processing and normalization The Dseq2 tool in the R programming language was used to standardize the raw data from GEO. The following analyses were carried out: fold change and P-value analysis, volcano plot, network analysis, GEPIA, and David pathway analysis. In this paper, using Venny software, we discovered 2 genes that are shared by neurotransmitters and NK cells in breast cancer and adrenal cancer. Between these genes and the pathways, they are a part of, we discovered a network. Pathway analysis revealed that these genes are mostly linked to the neurotransmitter and apoptotic pathways. In breast and adrenal tumors, the genes HRH1 and GABRD were discovered to be connected to NK cells. In response to breast and adrenal tumors, almost all of these genes are effective. It is thus postulated that the diagnosis of breast and adrenal cancer may be affected by the up-or down-regulation of these genes. Methods: Microarray gene expression data gene expression data was obtained from the Gene Expression Omnibus (GEO) Transcription 2 profile data of human NK cells from human breast and adrenal cancers were obtained from GEO (GSE179509 and GSE143383). Processing and normalization of data the raw data from GEO were normalized with the Dseq2 package in the R software. Fold change and P value analysis, Volcano plot, network analysis, GEPIA, and David pathway analysis were performed. Results: In this article, we found genes common to neurotransmitters with NK cells in adrenal cancer and breast cancer with Venny program, resulting in 2 genes. We identified a network between these genes and pathways they belong to. Pathway analysis showed that these genes are mostly associated with apoptosis and neurotransmitters pathway. Conclusion: HRH1 and GABRD genes were found to be associated with NK cells in breast and adrenal cancers. Almost all these genes are effective in response to breast and adrenal cancers. Therefore, it is hypothesized that downregulation or upregulation of these genes may affect breast and adrenal cancer diagnosis.展开更多
Objective To investigate changes in T lymphocyte subsets and NK cells in patients with simple Graves' disease(GD)and Graves' disease combined with type 2 diabetes mellitus(GD/T2DM).Methods Fifteen cases of GD/...Objective To investigate changes in T lymphocyte subsets and NK cells in patients with simple Graves' disease(GD)and Graves' disease combined with type 2 diabetes mellitus(GD/T2DM).Methods Fifteen cases of GD/T2DM were selected from our hospital from November 2001 to November 2004.Before and after therapy thyroid function,thyroglobulin antibody(TGA),thyroid microsomal antibody(TMA)and blood glucose level were measured,and T lymphocyte subsets(CD3,CD4,CD8,CD4/CD8)and NK cells(CD56)were measured by immunofluorescence double labeling monoclonal antibody and flow cytometry,respectively.At the same time,comparison was made with simple GD(15 cases),T2DM(15 cases)and healthy control(20 cases).Results Before therapy,CD4/CD8,CD4 and NK cells in GD/T2DM were less than normal,and there was no significant difference in comparison with simple GD(P<0.05).In T2DM group,only CD4/CD8 and CD4 were less than those of healthy controls(P<0.05).When thyroid function recovered after 1 to 3 months of methimazole treatment in both GD/T2DM and simple GD groups,various indexes recovered,which were more obvious in simple GD.Conclusion Immune hypofunction of GD may be the key to the immune abnormality of GD/T2DM,which is more significant than that of simple GD or T2DM.The recovery of thyroid function and immune abnormality is not consistent,and the recovery of GD is more significant than that of GD/T2DM.展开更多
Objective:To investigate the changes of Mg^(2+) levels in serum and peripheral blood mononuclear cells(PBMCs)of patients with COVID-19 and its effects on the functions of CD8^(+)T lymphocytes and NK cells.Methods:A to...Objective:To investigate the changes of Mg^(2+) levels in serum and peripheral blood mononuclear cells(PBMCs)of patients with COVID-19 and its effects on the functions of CD8^(+)T lymphocytes and NK cells.Methods:A total of 165 COVID-19 patients hospitalized in Ezhou Central Hospital from January 20 to February 20,2020 were divided into mild/common group(98 cases)and severe/critical group(67 cases).At the same time,34 healthy persons were selected as the control group.Peripheral blood was collected and PBMCs were isolated,the level of Mg^(2+) in serum and PBMCs was detected.The subsets of CD8^(+)T lymphocytes and NK cell and the expression levels of their surface inhibitory molecular PD-1 and activator molecular NKG2D were detected by flow cytometry.The correlation between Mg^(2+) concentration and the expression levels of PD-1 and NKG2D was also analyzed.Results:Compared with the control group,the concentration of Mg^(2+) in serum and PBMCs,the counts of CD8^(+)T lymphocytes and NK cell in patients with mild/common and severe/critical groups were significantly reduced(P<0.05),while the expression level of surface inhibitory molecular PD-1 were significantly increased(P<0.05),while the expression level of the activation molecule NKG2D were significantly decreased(P<0.05).However,the changes of the above indicators in patients with severe/critical group were greater than those in the mild/common group(P<0.05).In addition,the Mg^(2+) concentration in COVID-19 patients was negatively correlated with the expression level of PD-1 on CD8^(+)T lymphocytes and NK cells(P<0.05),and positively correlated with the expression levels of NKG2D(P<0.05).Conclusion:The concentration of Mg^(2+) in the serum and PBMCs of COVID-19 patients is significantly reduced,which may cause the function of CD8^(+)T lymphocytes and NK cells to be inhibited.展开更多
Severe fever with thrombocytopenia syndrome(SFTS)is an emerging infectious disease with high mortality(12%–30%).The mechanism by which the SFTS bunyavirus(SFTSV)causes severe illness remains unclear.To evaluate the p...Severe fever with thrombocytopenia syndrome(SFTS)is an emerging infectious disease with high mortality(12%–30%).The mechanism by which the SFTS bunyavirus(SFTSV)causes severe illness remains unclear.To evaluate the phenotypic and functional characteristics of the NK cell subsets in SFTS patients,twenty-nine SFTS patients were sequentially sampled from admission until recovery.Phenotypic and functional characteristics of NK cell subsets in circulating blood were analysed via flow cytometry.Then,correlations between NK cell subset frequencies and the SFTS index(SFTSI)were evaluated in all SFTS patients(15 mild,14 severe)upon admission.The frequencies of CD56dimCD16+NK cells were greatly decreased in early SFTSV infection and were negatively correlated with disease severity.Additionally,higher Ki-67 and granzyme B expression and relatively lower NKG2 A expression in CD56dimCD16+NK cells were observed in acute infection.Moreover,the effector function of CD56dimNK cells was increased in the acute phase compared with the recovery phase in nine severe SFTS patients.Additionally,interleukin(IL)-15,interferon(IFN)-a,IL-18 and IFN-c secretion was markedly increased during early infection.Collectively,despite depletion of CD56dimCD16+NK cells,activation and functional enhancement of CD56dimCD16+NK cells were still observed,suggesting their involvement in defence against early SFTSV infection.展开更多
NK cells play important roles in innate defenses against viruses and in the control of tumor growth and metastasis.The regulation/induction of NK cell function is mediated by an array of activating or inhibitory surfa...NK cells play important roles in innate defenses against viruses and in the control of tumor growth and metastasis.The regulation/induction of NK cell function is mediated by an array of activating or inhibitory surface receptors.In humans,major activating receptors involved in target cell killing are the natural cytotoxicity receptors(NCRs)and NKG2D.Activating receptors recognize ligands that are overexpressed or expressed de novo upon cell stress,viral infection,or tumor transformation.The HLA-class I-specific inhibitory receptors,including KIRs recognizing HLA-class I allotypic determinants and CD94/NKG2A recognizing the class-Ib HLA-E,constitute a fail-safe mechanism to avoid unwanted NK-mediated damage to healthy cells.Other receptors such as PD-1,primarily expressed by activated T lymphocytes,are important inhibitory checkpoints of immune responses that ensure T-cell tolerance.PD-1 also may be expressed by NK cells in cancer patients.Since PD-1 ligand(PD-L1)may be expressed by different tumors,PD-1/PD-L1 interactions inactivate both T and NK cells.Thus,the reliable evaluation of PD-L1 expression in tumors has become a major issue to select patients who may benefit from therapy with mAbs disrupting PD-1/PD-L1 interactions.Recently,NKG2A was revealed to be an important checkpoint controlling both NK and T-cell activation.Since most tumors express HLA-E,mAbs targeting NKG2A has been used alone or in combination with other therapeutic mAbs targeting PD-1 or tumor antigens(e.g.,EGFR),with encouraging results.The translational value of NK cells and their receptors is evidenced by the extraordinary therapeutic success of haploidentical HSCT to cure otherwise fatal high-risk leukemias.展开更多
Decidual macrophages (dMΦ) are distinct from the conventional macrophages present in other tissues and express M2macrophage markers, but the molecular mechanisms of formation and the roles of M2 MΦ during pregnancy ...Decidual macrophages (dMΦ) are distinct from the conventional macrophages present in other tissues and express M2macrophage markers, but the molecular mechanisms of formation and the roles of M2 MΦ during pregnancy have not beencompletely elucidated. The crosstalk between decidual natural killer cells (dNK) and dMΦ plays an important role in themaintenance of maternal–fetal immune tolerance. Here, CXCL16 derived from first-trimester trophoblast cells induces thepolarization of human M2 macrophages. The M2 MΦ polarized by CXCL16 exhibit decreased interleukin-15 production, whichfacilitates the inactivation of NK cells. The cytotoxicity of NK cells is attenuated by the CXCL16-polarized M2 MΦ. The data shown inthe present study provide evidence to support the hypothesis that CXCL16 secreted by trophoblast cells is a key molecule involvedin decidual M2 MΦ polarization, which in turn regulates the killing ability of NK cells, thereby contributing to the homeostatic andimmune-tolerant milieu required for successful fetal development.展开更多
Natural killer(NK) cells are important innate effectors that play a pivotal role in the defense against tumors and infections and participate in regulating adaptive immunity. Recent studies have revealed phenotypic an...Natural killer(NK) cells are important innate effectors that play a pivotal role in the defense against tumors and infections and participate in regulating adaptive immunity. Recent studies have revealed phenotypic and functional heterogeneity of NK cells.Here, using murine models of acute and chronic lymphocytic choriomeningitis virus infection, we observed that a CD49a^(+)CD49b^(+) NK cell subset emerged in the liver and other tissues, and underwent vigorous expansion following viral infection,before progressively decreasing in cell number. These viral infection-induced CD49a^(+)CD49b^(+) NK cells displayed an activated and mature phenotype. Moreover, compared with liver-resident NK cells and conventional NK(cNK) cells, CD49a^(+)CD49b^(+) NK cells showed increased functional competence, as evidenced by higher amounts of IFN-γ production and stronger cytotoxic capabilities during viral infection. Generation of these CD49a^(+)CD49b^(+) NK cells was shown to be independent of the T-bet transcription factor. Adoptive transfer experiments revealed that c NK cells could convert into CD49a^(+)CD49b^(+) NK cells following viral infection. Collectively, these results suggest that viral infection-induced CD49a^(+)CD49b^(+) NK cells represent a transiently activated state of cNK cells.展开更多
Objective To test NK cell quantities and function in patients with positive BMMNC-Coombs test(CBCPC)and cytopenia and to explore how NK cell participate in the progress of this disease.Methods The percentage of CD3-CD...Objective To test NK cell quantities and function in patients with positive BMMNC-Coombs test(CBCPC)and cytopenia and to explore how NK cell participate in the progress of this disease.Methods The percentage of CD3-CD56+NK cell in peripheral blood lymphocytes,the expression of activating receptor(NKG2D,NKp46,NKp44),inhibitory receptor(CD158a,CD158b),per-展开更多
Pregnancy is a complex physiological process involving several interconnected systems. Many researchers were concerned that the formation of a fetus with different genetic components may contradict the normal state of...Pregnancy is a complex physiological process involving several interconnected systems. Many researchers were concerned that the formation of a fetus with different genetic components may contradict the normal state of immunity, which attempts to reject and fight foreign bodies. This piqued the interest of biologists and immunologists, who set out to discover the immune system’s composition and mode of response in the uterus. According to several studies, natural killer (NK) cells are present in a significant percentage that differs from what is seen in peripheral blood. As a result, several scientific studies have been conducted on uterine NK cells, investigating their types, characteristics, receptors, secretions, and interactions with the surrounding environment. Research has also indicated the capacity of uterine NK cells to strike a balance between eradicating uterine infections and effectively contributing to different phases of pregnancy. Various studies have shown that NK cell activity is intimately related to the success or failure of pregnancy. In this review, we describe the uterine NK cell subtypes;decidual (dNK) cells and endometrial NK cells (eNK) cells and their important role during different phases of pregnancy.展开更多
Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its com...Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell activators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside IV,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory components of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.展开更多
BACKGROUND The incidence of intestinal NK/T cell lymphoma(NKTCL)is extremely low,and the clinical symptoms are atypical,which makes it difficult to distinguish this disorder from Crohn's disease(CD),T lymphocyte p...BACKGROUND The incidence of intestinal NK/T cell lymphoma(NKTCL)is extremely low,and the clinical symptoms are atypical,which makes it difficult to distinguish this disorder from Crohn's disease(CD),T lymphocyte proliferative disease,and other immune disorders.The misdiagnosis rate is high,and the patient's prognosis is poor.CASE SUMMARY In this case,the patient had repeated high fever,colonoscopy revealed multiple ulcers,and the initial diagnosis was CD.The patient’s condition did not improve after treatment with hormones and infliximab,and she eventually died.Positron emission tomographic-computed tomographic and B-ultrasound were performed in our hospital and showed that multiple lymph nodes were enlarged.Immunohistochemi-stry showed that CD3 and Epstein-Barr virus encoded RNA expression was positive.Colonoscopy,tissue biopsy,and histopathology showed intestinal focal mucosal infiltration of heterotypic lymphocytes with an abnormal immune phenotype.On the basis of the patient’s medical history,auxiliary examination,and pathological findings,digestive physicians and pathologists gave the diagnosis of NKTCL.CONCLUSION Clinicians need to improve their comprehensive knowledge of NKTCL,and combination of clinical symptoms,histological characteristics,as well as colonoscopy biopsies should be considered to improve the diagnosis and thereby reduce misdiagnosis.展开更多
This study reported two cases of Thai cancer patients, including a 36-year-old female with thyroid cancer of more than 5 years and a 64-year-old male with lung and colon cancers of more than 10 years. The written info...This study reported two cases of Thai cancer patients, including a 36-year-old female with thyroid cancer of more than 5 years and a 64-year-old male with lung and colon cancers of more than 10 years. The written informed consent was provided for autologous natural killer (NK) cell infusion at the anti-ageing and regenerative medicines clinic. Briefly, the blood was taken from the patient for NK cell count and their cytotoxic activity. Then, the patient’s NK cells were expanded </span><i><span style="font-family:Verdana;">in vitro</span></i><span style="font-family:Verdana;">, characterized and then counted before being delivered to the same patient by a single intravenous infusion. The vital signs and general physical examinations were observed for 2</span></span><span style="font-family:""> </span><span style="font-family:Verdana;">-</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">6 hours after the infusion. The patients were discharged if there were no adverse effects. The data showed the increasing number of NK cells and level of cytotoxic activity after the NK cell treatment, compared to the pre-treatment. In addition, the increasing total live cell concentration, as identified by the high percentage of CD56</span><sup><span style="font-family:Verdana;">dim</span></sup><span style="font-family:Verdana;">/CD16</span><sup><span style="font-family:Verdana;">bright</span></sup><span style="font-family:Verdana;"> cytotoxic NK cells, at day 21 of the NK cell expansion was consistent with the increasing cytotoxic activity of the patients after the treatment. Here, we demonstrated that this autologous NK cell therapy might be feasible;however, the study did not aim to evaluate the anti-cancer effect.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
Natural killer(NK)cell-based immunotherapies are attracting increasing interest in the field of cancer treatment.Early clinical trials have shown promising outcomes,alongside satisfactory product efficacy and safety.R...Natural killer(NK)cell-based immunotherapies are attracting increasing interest in the field of cancer treatment.Early clinical trials have shown promising outcomes,alongside satisfactory product efficacy and safety.Recent developments have greatly increased the therapeutic potential of NK cells by endowing them with enhanced recognition and cytotoxic capacities.This review focuses on surface receptor engineering in NK cell therapy and discusses its impact,challenges,and future directions.Most approaches are based on engineering with chimeric antigen receptors to allow NK cells to target specific tumor antigens independent of human leukocyte antigen restriction.This approach has increased the precision and potency of NK-mediated recognition and elimination of cancer cells.In addition,engineering NK cells with T-cell receptors also mediates the recognition of intracellular epitopes,which broadens the range of target peptides.Indirect tumor peptide recognition by NK cells has also been improved by optimizing immunoglobulin constant fragment receptor expression and signaling.Indeed,engineered NK cells have an improved ability to recognize and destroy target cells coated with specific antibodies,thereby increasing their antibodydependent cellular cytotoxicity.The ability of NK cell receptor engineering to promote the expansion,persistence,and infiltration of transferred cells in the tumor microenvironment has also been explored.Receptor-based strategies for sustained NK cell functionality within the tumor environment have also been discussed,and these strategies providing perspectives to counteract tumor-induced immunosuppression.Overall,receptor engineering has led to significant advances in NK cell-based cancer immunotherapies.As technical challenges are addressed,these innovative treatments will likely reshape cancer immunotherapy.展开更多
Circulating tumor cells(CTCs)are important biomarkers in the development and progression of lung cancer because they can reach other organs through the blood circulation and form distant metastases,exacerbating lung c...Circulating tumor cells(CTCs)are important biomarkers in the development and progression of lung cancer because they can reach other organs through the blood circulation and form distant metastases,exacerbating lung cancer progression.The presence of CTCs is also the main reason for the failure of nanomedicine-based lung cancer treatments.Therefore,magnetic MoSe_(2) nanosheets loaded with programmed death-ligand 1(PD-L1),named PD-L1-MFP NS,were employed here to precisely capture lung cancer CTCs in the blood circulation through the tumor-targeting effect of PD-L1 killing CTCs with highly effective photothermal therapy(PTT).In addition,by increasing the expression of cytomegalovirus UL16-binding protein(ULBP)ligands on tumor cells,the PD-L1-MFP NS further activated natural killer(NK)cells and triggered NK cell-induced cancer immunotherapy,thereby enhancing the overall tumor-killing effect.In summary,this material designed to capture CTCs provides a substantial advancement for personalized PTT-triggered immunotherapy and has great clinical translational potential.展开更多
Objective Interferon-induced transmembrane protein 3(IFITM3)is an important member of the IFITM family.However,the molecular mechanisms underlying its antiviral action have not been completely elucidated.Recent studie...Objective Interferon-induced transmembrane protein 3(IFITM3)is an important member of the IFITM family.However,the molecular mechanisms underlying its antiviral action have not been completely elucidated.Recent studies on IFITM3,particularly those focused on innate antiviral defense mechanisms,have shown that IFITM3 affects the body’s adaptive immune response.The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection in vivo.Methods We performed proteomics,flow cytometry,and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer(NK)cell numbers,their activation,and their immune function in the lungs of Ifitm3-/-and wild-type mice.Results Ifitm3-/-mice developed more severe inflammation and apoptotic responses compared to wild-type mice.Moreover,the NK cell activation was higher in the lungs of Ifitm3-/-mice during acute influenza infection.Conclusions Based on our results,we speculate that the NK cells are more readily activated in the absence of IFITM3,increasing mortality in Ifitm3-/-mice.展开更多
The tumor microenvironment is an ecosystem composed of multiple types of cells, such as tumor cells, immune cells, and cancerassociated fibroblasts. Cancer cells grow faster than non-cancerous cells and consume larger...The tumor microenvironment is an ecosystem composed of multiple types of cells, such as tumor cells, immune cells, and cancerassociated fibroblasts. Cancer cells grow faster than non-cancerous cells and consume larger amounts of nutrients. The rapid growth characteristic of cancer cells fundamentally alters nutrient availability in the tumor microenvironment and results in reprogramming of immune cell metabolic pathways. Accumulating evidence suggests that cellular metabolism of nutrients, such as lipids and amino acids, beyond being essential to meet the bioenergetic and biosynthetic demands of immune cells, also regulates a broad spectrum of cellular signal transduction, and influences immune cell survival, differentiation, and anti-tumor effector function. The cancer immunometabolism research field is rapidly evolving, and exciting new discoveries are reported in high-profile journals nearly weekly. Therefore, all new findings in this field cannot be summarized within this short review. Instead, this review is intended to provide a brief introduction to this rapidly developing research field, with a focus on the metabolism of two classes of important nutrients-lipids and amino acids-in immune cells. We highlight recent research on the roles of lipids and amino acids in regulating the metabolic fitness and immunological functions of T cells, macrophages, and natural killer cells in the tumor microenvironment. Furthermore, we discuss the possibility of “editing” metabolic pathways in immune cells to act synergistically with currently available immunotherapies in enhancing anti-tumor immune responses.展开更多
The signaling lymphocyte activation molecule(SLAM)family of receptors(SFRs)are ubiquitously expressed on immune cells,and they regulate multiple immune events by recruiting SH2(Src homology 2)domain-containing SAP fam...The signaling lymphocyte activation molecule(SLAM)family of receptors(SFRs)are ubiquitously expressed on immune cells,and they regulate multiple immune events by recruiting SH2(Src homology 2)domain-containing SAP family adapters,including SAP and its homologs,Ewing’s sarcoma-associated transcript 2(EAT-2)and EAT-2 related transducer(ERT).In human patients with X-linked lymphoproliferative(XLP)disease,which is caused by SAP mutations,SFRs alternatively bind other inhibitory SH2 domain-containing molecules to suppress immune cell activation and development.NK cells express multiple SFRs and all SAP family adapters.In recent decades,SFRs have been found to be critical for enhancing NK cell activation in response to abnormal hematopoietic cells in SAP-family-intact NK cells;however,SFRs might suppress NK cell activation in SAP-family-deficient mice or patients with XLP1.In this paper,we review how these two distinct SFR signaling pathways orchestrate NK cell activation and inhibition and highlight the importance of SFR regulation of NK cell biology and their physiological status and pathological relevance in patients with XLP1.展开更多
Natural killer(NK)cells are thought to play a key role in the successful establishment of a pregnancy by facilitating immunological adaptation of the semi-allogeneic developing embryo.The aim of this study was to expl...Natural killer(NK)cells are thought to play a key role in the successful establishment of a pregnancy by facilitating immunological adaptation of the semi-allogeneic developing embryo.The aim of this study was to explore the cell number,immunophenotypic characteristics,and activities of peripheral blood NK cells in women with repeated implantation failure(RIF).Peripheral blood was obtained from 27 women with RIF and 11 healthy,fertile controls during the middle luteal phase of the menstrual cycle.CD3^-CD56^+NK cells were quantified and analyzed by flow cytometry for the expression of cytolytic molecules(granzyme B,granulysin,and perforin)as well as cell surface receptors responsible for NK cell activation or inhibition(NKG2D,NKp30,NKp46,CD158a,CD158b).NK cytotoxicity was measured at three effector-to-target cell ratios.Women with RIF and fertile controls did not differ significantly in the percentage of circulating CD3CD56t NK cells,or in the proportions of these cells that expressed granzyme B,granulysin,or perforin.The two groups also did not differ significantly in the proportions of NK cells expressing the receptors NKG2D,NKp30,NKp46,CD158a or CD158b.General linear model analysis showed that NK cytotoxicity increased with effector-to-target cell ratio.However,NK cytotoxicity did not differ significantly between patients with RIF and fertile controls.These results suggest that RIF is not associated with significant alterations in the number or function of peripheral blood NK cells.展开更多
文摘Purpose: Data on microarray gene expression The Gene Expression Omnibus (GEO) provided information on gene expression. Transcription GEO provided two profiles of human NK cells from breast and adrenal tumors (GSE179509 and GSE143383). Data processing and normalization The Dseq2 tool in the R programming language was used to standardize the raw data from GEO. The following analyses were carried out: fold change and P-value analysis, volcano plot, network analysis, GEPIA, and David pathway analysis. In this paper, using Venny software, we discovered 2 genes that are shared by neurotransmitters and NK cells in breast cancer and adrenal cancer. Between these genes and the pathways, they are a part of, we discovered a network. Pathway analysis revealed that these genes are mostly linked to the neurotransmitter and apoptotic pathways. In breast and adrenal tumors, the genes HRH1 and GABRD were discovered to be connected to NK cells. In response to breast and adrenal tumors, almost all of these genes are effective. It is thus postulated that the diagnosis of breast and adrenal cancer may be affected by the up-or down-regulation of these genes. Methods: Microarray gene expression data gene expression data was obtained from the Gene Expression Omnibus (GEO) Transcription 2 profile data of human NK cells from human breast and adrenal cancers were obtained from GEO (GSE179509 and GSE143383). Processing and normalization of data the raw data from GEO were normalized with the Dseq2 package in the R software. Fold change and P value analysis, Volcano plot, network analysis, GEPIA, and David pathway analysis were performed. Results: In this article, we found genes common to neurotransmitters with NK cells in adrenal cancer and breast cancer with Venny program, resulting in 2 genes. We identified a network between these genes and pathways they belong to. Pathway analysis showed that these genes are mostly associated with apoptosis and neurotransmitters pathway. Conclusion: HRH1 and GABRD genes were found to be associated with NK cells in breast and adrenal cancers. Almost all these genes are effective in response to breast and adrenal cancers. Therefore, it is hypothesized that downregulation or upregulation of these genes may affect breast and adrenal cancer diagnosis.
基金the Scientific and Technological Development Foundation of Baotou Medical Science in Inner Mongolia [(2001) No.198]
文摘Objective To investigate changes in T lymphocyte subsets and NK cells in patients with simple Graves' disease(GD)and Graves' disease combined with type 2 diabetes mellitus(GD/T2DM).Methods Fifteen cases of GD/T2DM were selected from our hospital from November 2001 to November 2004.Before and after therapy thyroid function,thyroglobulin antibody(TGA),thyroid microsomal antibody(TMA)and blood glucose level were measured,and T lymphocyte subsets(CD3,CD4,CD8,CD4/CD8)and NK cells(CD56)were measured by immunofluorescence double labeling monoclonal antibody and flow cytometry,respectively.At the same time,comparison was made with simple GD(15 cases),T2DM(15 cases)and healthy control(20 cases).Results Before therapy,CD4/CD8,CD4 and NK cells in GD/T2DM were less than normal,and there was no significant difference in comparison with simple GD(P<0.05).In T2DM group,only CD4/CD8 and CD4 were less than those of healthy controls(P<0.05).When thyroid function recovered after 1 to 3 months of methimazole treatment in both GD/T2DM and simple GD groups,various indexes recovered,which were more obvious in simple GD.Conclusion Immune hypofunction of GD may be the key to the immune abnormality of GD/T2DM,which is more significant than that of simple GD or T2DM.The recovery of thyroid function and immune abnormality is not consistent,and the recovery of GD is more significant than that of GD/T2DM.
文摘Objective:To investigate the changes of Mg^(2+) levels in serum and peripheral blood mononuclear cells(PBMCs)of patients with COVID-19 and its effects on the functions of CD8^(+)T lymphocytes and NK cells.Methods:A total of 165 COVID-19 patients hospitalized in Ezhou Central Hospital from January 20 to February 20,2020 were divided into mild/common group(98 cases)and severe/critical group(67 cases).At the same time,34 healthy persons were selected as the control group.Peripheral blood was collected and PBMCs were isolated,the level of Mg^(2+) in serum and PBMCs was detected.The subsets of CD8^(+)T lymphocytes and NK cell and the expression levels of their surface inhibitory molecular PD-1 and activator molecular NKG2D were detected by flow cytometry.The correlation between Mg^(2+) concentration and the expression levels of PD-1 and NKG2D was also analyzed.Results:Compared with the control group,the concentration of Mg^(2+) in serum and PBMCs,the counts of CD8^(+)T lymphocytes and NK cell in patients with mild/common and severe/critical groups were significantly reduced(P<0.05),while the expression level of surface inhibitory molecular PD-1 were significantly increased(P<0.05),while the expression level of the activation molecule NKG2D were significantly decreased(P<0.05).However,the changes of the above indicators in patients with severe/critical group were greater than those in the mild/common group(P<0.05).In addition,the Mg^(2+) concentration in COVID-19 patients was negatively correlated with the expression level of PD-1 on CD8^(+)T lymphocytes and NK cells(P<0.05),and positively correlated with the expression levels of NKG2D(P<0.05).Conclusion:The concentration of Mg^(2+) in the serum and PBMCs of COVID-19 patients is significantly reduced,which may cause the function of CD8^(+)T lymphocytes and NK cells to be inhibited.
基金supported by the National Natural Science Foundation of China(81271884)and of Hubei(2018CFB471)
文摘Severe fever with thrombocytopenia syndrome(SFTS)is an emerging infectious disease with high mortality(12%–30%).The mechanism by which the SFTS bunyavirus(SFTSV)causes severe illness remains unclear.To evaluate the phenotypic and functional characteristics of the NK cell subsets in SFTS patients,twenty-nine SFTS patients were sequentially sampled from admission until recovery.Phenotypic and functional characteristics of NK cell subsets in circulating blood were analysed via flow cytometry.Then,correlations between NK cell subset frequencies and the SFTS index(SFTSI)were evaluated in all SFTS patients(15 mild,14 severe)upon admission.The frequencies of CD56dimCD16+NK cells were greatly decreased in early SFTSV infection and were negatively correlated with disease severity.Additionally,higher Ki-67 and granzyme B expression and relatively lower NKG2 A expression in CD56dimCD16+NK cells were observed in acute infection.Moreover,the effector function of CD56dimNK cells was increased in the acute phase compared with the recovery phase in nine severe SFTS patients.Additionally,interleukin(IL)-15,interferon(IFN)-a,IL-18 and IFN-c secretion was markedly increased during early infection.Collectively,despite depletion of CD56dimCD16+NK cells,activation and functional enhancement of CD56dimCD16+NK cells were still observed,suggesting their involvement in defence against early SFTSV infection.
文摘NK cells play important roles in innate defenses against viruses and in the control of tumor growth and metastasis.The regulation/induction of NK cell function is mediated by an array of activating or inhibitory surface receptors.In humans,major activating receptors involved in target cell killing are the natural cytotoxicity receptors(NCRs)and NKG2D.Activating receptors recognize ligands that are overexpressed or expressed de novo upon cell stress,viral infection,or tumor transformation.The HLA-class I-specific inhibitory receptors,including KIRs recognizing HLA-class I allotypic determinants and CD94/NKG2A recognizing the class-Ib HLA-E,constitute a fail-safe mechanism to avoid unwanted NK-mediated damage to healthy cells.Other receptors such as PD-1,primarily expressed by activated T lymphocytes,are important inhibitory checkpoints of immune responses that ensure T-cell tolerance.PD-1 also may be expressed by NK cells in cancer patients.Since PD-1 ligand(PD-L1)may be expressed by different tumors,PD-1/PD-L1 interactions inactivate both T and NK cells.Thus,the reliable evaluation of PD-L1 expression in tumors has become a major issue to select patients who may benefit from therapy with mAbs disrupting PD-1/PD-L1 interactions.Recently,NKG2A was revealed to be an important checkpoint controlling both NK and T-cell activation.Since most tumors express HLA-E,mAbs targeting NKG2A has been used alone or in combination with other therapeutic mAbs targeting PD-1 or tumor antigens(e.g.,EGFR),with encouraging results.The translational value of NK cells and their receptors is evidenced by the extraordinary therapeutic success of haploidentical HSCT to cure otherwise fatal high-risk leukemias.
基金This study was funded by grant number MOST 2015CB943300 awarded to Da-Jin Lia grant from the National Natural Science Foundation of China,number 81200425,awarded to Xiao-Qiu Wang+2 种基金a grant from the National Natural Science Foundation of China,number 81471548,awarded to D.-J.L.a grant from the National Natural Science Foundation of China,number 81571512,awarded to Q.F.a grant from The Department of Science and Technology in Shandong Province,number ZR2015JL027,awarded to Q.F.
文摘Decidual macrophages (dMΦ) are distinct from the conventional macrophages present in other tissues and express M2macrophage markers, but the molecular mechanisms of formation and the roles of M2 MΦ during pregnancy have not beencompletely elucidated. The crosstalk between decidual natural killer cells (dNK) and dMΦ plays an important role in themaintenance of maternal–fetal immune tolerance. Here, CXCL16 derived from first-trimester trophoblast cells induces thepolarization of human M2 macrophages. The M2 MΦ polarized by CXCL16 exhibit decreased interleukin-15 production, whichfacilitates the inactivation of NK cells. The cytotoxicity of NK cells is attenuated by the CXCL16-polarized M2 MΦ. The data shown inthe present study provide evidence to support the hypothesis that CXCL16 secreted by trophoblast cells is a key molecule involvedin decidual M2 MΦ polarization, which in turn regulates the killing ability of NK cells, thereby contributing to the homeostatic andimmune-tolerant milieu required for successful fetal development.
基金supported by the National Natural Science Foundation of China (81788101, 81761128013, 81571522, 91642105, 81821001, 91542000)。
文摘Natural killer(NK) cells are important innate effectors that play a pivotal role in the defense against tumors and infections and participate in regulating adaptive immunity. Recent studies have revealed phenotypic and functional heterogeneity of NK cells.Here, using murine models of acute and chronic lymphocytic choriomeningitis virus infection, we observed that a CD49a^(+)CD49b^(+) NK cell subset emerged in the liver and other tissues, and underwent vigorous expansion following viral infection,before progressively decreasing in cell number. These viral infection-induced CD49a^(+)CD49b^(+) NK cells displayed an activated and mature phenotype. Moreover, compared with liver-resident NK cells and conventional NK(cNK) cells, CD49a^(+)CD49b^(+) NK cells showed increased functional competence, as evidenced by higher amounts of IFN-γ production and stronger cytotoxic capabilities during viral infection. Generation of these CD49a^(+)CD49b^(+) NK cells was shown to be independent of the T-bet transcription factor. Adoptive transfer experiments revealed that c NK cells could convert into CD49a^(+)CD49b^(+) NK cells following viral infection. Collectively, these results suggest that viral infection-induced CD49a^(+)CD49b^(+) NK cells represent a transiently activated state of cNK cells.
文摘Objective To test NK cell quantities and function in patients with positive BMMNC-Coombs test(CBCPC)and cytopenia and to explore how NK cell participate in the progress of this disease.Methods The percentage of CD3-CD56+NK cell in peripheral blood lymphocytes,the expression of activating receptor(NKG2D,NKp46,NKp44),inhibitory receptor(CD158a,CD158b),per-
文摘Pregnancy is a complex physiological process involving several interconnected systems. Many researchers were concerned that the formation of a fetus with different genetic components may contradict the normal state of immunity, which attempts to reject and fight foreign bodies. This piqued the interest of biologists and immunologists, who set out to discover the immune system’s composition and mode of response in the uterus. According to several studies, natural killer (NK) cells are present in a significant percentage that differs from what is seen in peripheral blood. As a result, several scientific studies have been conducted on uterine NK cells, investigating their types, characteristics, receptors, secretions, and interactions with the surrounding environment. Research has also indicated the capacity of uterine NK cells to strike a balance between eradicating uterine infections and effectively contributing to different phases of pregnancy. Various studies have shown that NK cell activity is intimately related to the success or failure of pregnancy. In this review, we describe the uterine NK cell subtypes;decidual (dNK) cells and endometrial NK cells (eNK) cells and their important role during different phases of pregnancy.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82073814,81973291,82122066,and 82003909)the Rising-Star Program of Shanghai Science and Technology Committee(Grant No.:19QA1411500).
文摘Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell activators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside IV,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory components of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.
文摘BACKGROUND The incidence of intestinal NK/T cell lymphoma(NKTCL)is extremely low,and the clinical symptoms are atypical,which makes it difficult to distinguish this disorder from Crohn's disease(CD),T lymphocyte proliferative disease,and other immune disorders.The misdiagnosis rate is high,and the patient's prognosis is poor.CASE SUMMARY In this case,the patient had repeated high fever,colonoscopy revealed multiple ulcers,and the initial diagnosis was CD.The patient’s condition did not improve after treatment with hormones and infliximab,and she eventually died.Positron emission tomographic-computed tomographic and B-ultrasound were performed in our hospital and showed that multiple lymph nodes were enlarged.Immunohistochemi-stry showed that CD3 and Epstein-Barr virus encoded RNA expression was positive.Colonoscopy,tissue biopsy,and histopathology showed intestinal focal mucosal infiltration of heterotypic lymphocytes with an abnormal immune phenotype.On the basis of the patient’s medical history,auxiliary examination,and pathological findings,digestive physicians and pathologists gave the diagnosis of NKTCL.CONCLUSION Clinicians need to improve their comprehensive knowledge of NKTCL,and combination of clinical symptoms,histological characteristics,as well as colonoscopy biopsies should be considered to improve the diagnosis and thereby reduce misdiagnosis.
文摘This study reported two cases of Thai cancer patients, including a 36-year-old female with thyroid cancer of more than 5 years and a 64-year-old male with lung and colon cancers of more than 10 years. The written informed consent was provided for autologous natural killer (NK) cell infusion at the anti-ageing and regenerative medicines clinic. Briefly, the blood was taken from the patient for NK cell count and their cytotoxic activity. Then, the patient’s NK cells were expanded </span><i><span style="font-family:Verdana;">in vitro</span></i><span style="font-family:Verdana;">, characterized and then counted before being delivered to the same patient by a single intravenous infusion. The vital signs and general physical examinations were observed for 2</span></span><span style="font-family:""> </span><span style="font-family:Verdana;">-</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">6 hours after the infusion. The patients were discharged if there were no adverse effects. The data showed the increasing number of NK cells and level of cytotoxic activity after the NK cell treatment, compared to the pre-treatment. In addition, the increasing total live cell concentration, as identified by the high percentage of CD56</span><sup><span style="font-family:Verdana;">dim</span></sup><span style="font-family:Verdana;">/CD16</span><sup><span style="font-family:Verdana;">bright</span></sup><span style="font-family:Verdana;"> cytotoxic NK cells, at day 21 of the NK cell expansion was consistent with the increasing cytotoxic activity of the patients after the treatment. Here, we demonstrated that this autologous NK cell therapy might be feasible;however, the study did not aim to evaluate the anti-cancer effect.
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.
基金The AP postdoctoral position is funded by INCa PLBio 2020-095.
文摘Natural killer(NK)cell-based immunotherapies are attracting increasing interest in the field of cancer treatment.Early clinical trials have shown promising outcomes,alongside satisfactory product efficacy and safety.Recent developments have greatly increased the therapeutic potential of NK cells by endowing them with enhanced recognition and cytotoxic capacities.This review focuses on surface receptor engineering in NK cell therapy and discusses its impact,challenges,and future directions.Most approaches are based on engineering with chimeric antigen receptors to allow NK cells to target specific tumor antigens independent of human leukocyte antigen restriction.This approach has increased the precision and potency of NK-mediated recognition and elimination of cancer cells.In addition,engineering NK cells with T-cell receptors also mediates the recognition of intracellular epitopes,which broadens the range of target peptides.Indirect tumor peptide recognition by NK cells has also been improved by optimizing immunoglobulin constant fragment receptor expression and signaling.Indeed,engineered NK cells have an improved ability to recognize and destroy target cells coated with specific antibodies,thereby increasing their antibodydependent cellular cytotoxicity.The ability of NK cell receptor engineering to promote the expansion,persistence,and infiltration of transferred cells in the tumor microenvironment has also been explored.Receptor-based strategies for sustained NK cell functionality within the tumor environment have also been discussed,and these strategies providing perspectives to counteract tumor-induced immunosuppression.Overall,receptor engineering has led to significant advances in NK cell-based cancer immunotherapies.As technical challenges are addressed,these innovative treatments will likely reshape cancer immunotherapy.
基金supported by the National Natural Science Fund for Distinguished Young Scholars(No.82225025)the National Natural Science Foundation of China(Nos.21877049,32171296)+1 种基金China Postdoctoral Science Foundation(No.2021M690066)Guangdong Basic and Applied Basic Research Foundation(No.2021A1515110300).
文摘Circulating tumor cells(CTCs)are important biomarkers in the development and progression of lung cancer because they can reach other organs through the blood circulation and form distant metastases,exacerbating lung cancer progression.The presence of CTCs is also the main reason for the failure of nanomedicine-based lung cancer treatments.Therefore,magnetic MoSe_(2) nanosheets loaded with programmed death-ligand 1(PD-L1),named PD-L1-MFP NS,were employed here to precisely capture lung cancer CTCs in the blood circulation through the tumor-targeting effect of PD-L1 killing CTCs with highly effective photothermal therapy(PTT).In addition,by increasing the expression of cytomegalovirus UL16-binding protein(ULBP)ligands on tumor cells,the PD-L1-MFP NS further activated natural killer(NK)cells and triggered NK cell-induced cancer immunotherapy,thereby enhancing the overall tumor-killing effect.In summary,this material designed to capture CTCs provides a substantial advancement for personalized PTT-triggered immunotherapy and has great clinical translational potential.
基金supported by the National Science Fund for Distinguished Young Scholars of China[Grant No.81525017]National Natural Youth Science Foundation[Grant No.31900140]。
文摘Objective Interferon-induced transmembrane protein 3(IFITM3)is an important member of the IFITM family.However,the molecular mechanisms underlying its antiviral action have not been completely elucidated.Recent studies on IFITM3,particularly those focused on innate antiviral defense mechanisms,have shown that IFITM3 affects the body’s adaptive immune response.The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection in vivo.Methods We performed proteomics,flow cytometry,and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer(NK)cell numbers,their activation,and their immune function in the lungs of Ifitm3-/-and wild-type mice.Results Ifitm3-/-mice developed more severe inflammation and apoptotic responses compared to wild-type mice.Moreover,the NK cell activation was higher in the lungs of Ifitm3-/-mice during acute influenza infection.Conclusions Based on our results,we speculate that the NK cells are more readily activated in the absence of IFITM3,increasing mortality in Ifitm3-/-mice.
基金supported by a CRI Lloyd J. Old STAR Award(Grant No. 3914)a Helmholtz Young Investigator Award(Grant No. VH-NG-1113)+7 种基金an EMBO Young Investigator Awardan Exploration Grant of the Boehringer Ingelheim Foundation (BIS)the German Research Foundation (DFG,Grant Nos. CU375/5-1, CU375/5-2, CU375/7-1, CU375/9-1, and 259332240/RTG2099)the German Cancer Aid Foundation (DKH, Grant Nos. 70113343 and 70114224)the Helmholtz Zukunftsthema Ageing and Metabolic Programming (AMPro, Grant No. ZT0026)HI-TRON KickStart Seed Funding (Grant No. HITR-2021-08)the Hector Foundation (Grant No. M20102)an ERC Consolidator Award (Grant No. 101045416)
文摘The tumor microenvironment is an ecosystem composed of multiple types of cells, such as tumor cells, immune cells, and cancerassociated fibroblasts. Cancer cells grow faster than non-cancerous cells and consume larger amounts of nutrients. The rapid growth characteristic of cancer cells fundamentally alters nutrient availability in the tumor microenvironment and results in reprogramming of immune cell metabolic pathways. Accumulating evidence suggests that cellular metabolism of nutrients, such as lipids and amino acids, beyond being essential to meet the bioenergetic and biosynthetic demands of immune cells, also regulates a broad spectrum of cellular signal transduction, and influences immune cell survival, differentiation, and anti-tumor effector function. The cancer immunometabolism research field is rapidly evolving, and exciting new discoveries are reported in high-profile journals nearly weekly. Therefore, all new findings in this field cannot be summarized within this short review. Instead, this review is intended to provide a brief introduction to this rapidly developing research field, with a focus on the metabolism of two classes of important nutrients-lipids and amino acids-in immune cells. We highlight recent research on the roles of lipids and amino acids in regulating the metabolic fitness and immunological functions of T cells, macrophages, and natural killer cells in the tumor microenvironment. Furthermore, we discuss the possibility of “editing” metabolic pathways in immune cells to act synergistically with currently available immunotherapies in enhancing anti-tumor immune responses.
基金Research in Dong’s lab was supported by the Natural Science Foundation of China(to Z.D.,81725007,31830027,and 31821003)National Key Research and Develop-ment Program(2018YFC1003900 to Z.D)+2 种基金Beijing Natural Science Foundation(5172018 to Z.D.)the Postdoctoral Innovation Talent Support Program of China(to S.C.,BX201700134)the China Postdoctoral Science Foundation grant(to S.C.,2017M620051).
文摘The signaling lymphocyte activation molecule(SLAM)family of receptors(SFRs)are ubiquitously expressed on immune cells,and they regulate multiple immune events by recruiting SH2(Src homology 2)domain-containing SAP family adapters,including SAP and its homologs,Ewing’s sarcoma-associated transcript 2(EAT-2)and EAT-2 related transducer(ERT).In human patients with X-linked lymphoproliferative(XLP)disease,which is caused by SAP mutations,SFRs alternatively bind other inhibitory SH2 domain-containing molecules to suppress immune cell activation and development.NK cells express multiple SFRs and all SAP family adapters.In recent decades,SFRs have been found to be critical for enhancing NK cell activation in response to abnormal hematopoietic cells in SAP-family-intact NK cells;however,SFRs might suppress NK cell activation in SAP-family-deficient mice or patients with XLP1.In this paper,we review how these two distinct SFR signaling pathways orchestrate NK cell activation and inhibition and highlight the importance of SFR regulation of NK cell biology and their physiological status and pathological relevance in patients with XLP1.
基金This work was supported by the Shenzhen Healthcare Research Project,China(SZXJ2018004)Clinical Research Program of Chinese Medical Association,China(17020340703)the Sanming Project of Medicine in Shenzhen,China(SZSM201502035).
文摘Natural killer(NK)cells are thought to play a key role in the successful establishment of a pregnancy by facilitating immunological adaptation of the semi-allogeneic developing embryo.The aim of this study was to explore the cell number,immunophenotypic characteristics,and activities of peripheral blood NK cells in women with repeated implantation failure(RIF).Peripheral blood was obtained from 27 women with RIF and 11 healthy,fertile controls during the middle luteal phase of the menstrual cycle.CD3^-CD56^+NK cells were quantified and analyzed by flow cytometry for the expression of cytolytic molecules(granzyme B,granulysin,and perforin)as well as cell surface receptors responsible for NK cell activation or inhibition(NKG2D,NKp30,NKp46,CD158a,CD158b).NK cytotoxicity was measured at three effector-to-target cell ratios.Women with RIF and fertile controls did not differ significantly in the percentage of circulating CD3CD56t NK cells,or in the proportions of these cells that expressed granzyme B,granulysin,or perforin.The two groups also did not differ significantly in the proportions of NK cells expressing the receptors NKG2D,NKp30,NKp46,CD158a or CD158b.General linear model analysis showed that NK cytotoxicity increased with effector-to-target cell ratio.However,NK cytotoxicity did not differ significantly between patients with RIF and fertile controls.These results suggest that RIF is not associated with significant alterations in the number or function of peripheral blood NK cells.
