BACKGROUND Liver failure has high mortality and poor prognosis,and establishing new reliable markers for predicting its prognosis is necessary.Mucosal-associated invariant T(MAIT)cells are a novel population of innate...BACKGROUND Liver failure has high mortality and poor prognosis,and establishing new reliable markers for predicting its prognosis is necessary.Mucosal-associated invariant T(MAIT)cells are a novel population of innate-like lymphocytes involved in inflammatory liver disease,and their potential role in liver failure remains unclear.AIM To investigate alteration of circulating MAIT cells and assess its prognostic value in patients with hepatitis B virus(HBV)-related liver failure.METHODS We recruited 55 patients with HBV-related liver failure,48 patients with chronic hepatitis B and 40 healthy controls(HCs)from Nantong Third People’s Hospital Affiliated to Nantong University.Peripheral blood mononuclear cells were isolated,and the percentage and number of circulating MAIT cells were detected by flow cytometry.Plasma levels of interleukin(IL)-7,IL-12p70,IL-18 and interferon-αwere measured by Luminex assay.RESULTS Circulating MAIT cells were significantly decreased in HBV-related liver failure patients(percentage:2.00±1.22 vs 5.19±1.27%,P<0.0001;number:5.47±4.93 vs 84.43±19.59,P<0.0001)compared with HCs.More importantly,there was a significant reduction of MAIT cells in patients with middle/late-stage compared with early-stage liver failure.Circulating MAIT cells partially recovered after disease improvement,both in percentage(4.01±1.21 vs 2.04±0.95%,P<0.0001)and in cell count(17.24±8.56 vs 7.41±4.99,P<0.0001).The proportion(2.29±1.01 vs 1.58±1.38%,P<0.05)and number(7.30±5.70 vs 2.94±1.47,P<0.001)of circulating MAIT cells were significantly higher in the survival group than in the dead/liver transplantation group,and the Kaplan–Meier curve showed that lower expression of circulating MAIT cells(both percentage and cell count)predicted poor overall survival(P<0.01).Also,the levels of IL-12(20.26±5.42 pg/mL vs 17.76±2.79 pg/mL,P=0.01)and IL-18(1470.05±1525.38 pg/mL vs 362.99±109.64 pg/mL,P<0.0001)were dramatically increased in HBV-related liver failure patients compared with HCs.CONCLUSION Circulating MAIT cells may play an important role in the process of HBV-related liver failure and can be an important prognostic marker.展开更多
Mice have frequently been used to model human diseases involving immune dysregulation such as autoimmune and inflammatory diseases.These models help elucidatethe mechanisms underlying the disease and in the developmen...Mice have frequently been used to model human diseases involving immune dysregulation such as autoimmune and inflammatory diseases.These models help elucidatethe mechanisms underlying the disease and in the development of novel therapies.However,if mice are deficient in certain cells and/or effectors associated with human diseases,how can their functions be investigated in this species?Mucosal-associated invariant T(MAIT)cells,a novel innate-like T cell family member,are a good example.MAIT cells are abundant in humans but scarce in laboratory mice.MAIT cells harbor an invariant T cell receptor and recognize nonpeptidic antigens vitamin B2metabolites from bacteria and yeasts.Recent studies have shown that MAIT cells play a pivotal role in human diseases such as bacterial infections and autoimmune and inflammatory diseases.MAIT cells possess granulysin,a human-specific effector molecule,but granulysin and its homologue are absent in mice.Furthermore,MAIT cells show poor proliferation in vitro.To overcome these problems and further our knowledge of MAIT cells,we have established a method to expand MAIT cells via induced pluripotent stem cells(iP SCs).In this review,we describe recent advances in the field of MAIT cell research and our approach for human disease modeling with iP SCderived MAIT cells.展开更多
Mucosal-associated invariant T(MAIT)cells have been described in liver and nonliver diseases,and they have been ascribed antimicrobial,immune regulatory,protective,and pathogenic roles.The goals of this review are to ...Mucosal-associated invariant T(MAIT)cells have been described in liver and nonliver diseases,and they have been ascribed antimicrobial,immune regulatory,protective,and pathogenic roles.The goals of this review are to describe their biological properties,indicate their involvement in chronic liver disease,and encourage investigations that clarify their actions and therapeutic implications.English abstracts were identified in PubMed by multiple search terms,and bibliographies were developed.MAIT cells are activated by restricted non-peptides of limited diversity and by multiple inflammatory cytokines.Diverse pro-inflammatory,anti-inflammatory,and immune regulatory cytokines are released;infected cells are eliminated;and memory cells emerge.Circulating MAIT cells are hyper-activated,immune exhausted,dysfunctional,and depleted in chronic liver disease.This phenotype lacks disease-specificity,and it does not predict the biological effects.MAIT cells have presumed protective actions in chronic viral hepatitis,alcoholic hepatitis,non-alcoholic fatty liver disease,primary sclerosing cholangitis,and decompensated cirrhosis.They have pathogenic and pro-fibrotic actions in autoimmune hepatitis and mixed actions in primary biliary cholangitis.Local factors in the hepatic microenvironment(cytokines,bile acids,gut-derived bacterial antigens,and metabolic by-products)may modulate their response in individual diseases.Investigational manipulations of function are warranted to establish an association with disease severity and outcome.In conclusion,MAIT cells constitute a disease-nonspecific,immune response to chronic liver inflammation and infection.Their pathological role has been deduced from their deficiencies during active liver disease,and future investigations must clarify this role,link it to outcome,and explore therapeutic interventions.展开更多
Opportunistic bacteria in apical periodontitis (AP) may pose a risk for systemic dissemination.Mucosal-associated invariant T (MAIT) cells are innate-like T cells with a broad and potent antimicrobial activity importa...Opportunistic bacteria in apical periodontitis (AP) may pose a risk for systemic dissemination.Mucosal-associated invariant T (MAIT) cells are innate-like T cells with a broad and potent antimicrobial activity important for gut mucosal integrity.It was recently shown that MAIT cells are present in the oral mucosal tissue,but the involvement of MAIT cells in AP is unknown.Here,comparison of surgically resected AP and gingival tissues demonstrated that AP tissues express significantly higher levels of Vα7.2-Jα33,Vα7.2- Jα20,Vα7.2-Jα12,Cα and tumour necrosis factor (TNF),interferon (IFN)-γ and interleukin (IL)-17A transcripts,resembling a MAIT cell signature.Moreover,in AP tissues the MR1-restricted MAIT cells positive for MR1–5-OP-RU tetramer staining appeared to be of similar levels as in peripheral blood but consisted mainly of CD4^+ subset.Unlike gingival tissues,the AP microbiome was quantitatively impacted by factors like fistula and high patient age and had a prominent riboflavin-expressing bacterial feature.When merged in an integrated view,the examined immune and microbiome data in the sparse partial least squares discriminant analysis could identify bacterial relative abundances that negatively correlated with Vα7.2-Jα33,Cα,and IL-17A transcript expressions in AP,implying that MAIT cells could play a role in the local defence at the oral tissue barrier.In conclusion,we describe the presence of MAIT cells at the oral site where translocation of oral microbiota could take place.These findings have implications for understanding the immune sensing of polymicrobial-related oral diseases.展开更多
Background: Mucosal-associated invariant T(MAIT) cells are systemically depleted in human immunodeficiency virus type 1(HIV-1) infected patients and are not replenished even after successful combined antiretroviral th...Background: Mucosal-associated invariant T(MAIT) cells are systemically depleted in human immunodeficiency virus type 1(HIV-1) infected patients and are not replenished even after successful combined antiretroviral therapy(cART).This study aimed to identify the mechanism underlying MAIT cell depletion.Methods: In the present study, we applied flow cytometry, single-cell RNA sequencing and immunohistochemical staining to evaluate the characteristics of pyroptotic MAIT cells in a total of 127 HIV-1 infected individuals, including 69 treatment-naive patients, 28 complete responders, 15 immunological non-responders, and 15 elite controllers, at the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.Results: Single-cell transcriptomic profiles revealed that circulating MAIT cells from HIV-1 infected subjects were highly activated, with upregulation of pyroptosis-related genes. Further analysis revealed that increased frequencies of pyroptotic MAIT cells correlated with markers of systemic T-cell activation, microbial translocation, and intestinal damage in cART-naive patients and poor CD4+ T-cell recovery in long-term cART patients. Immunohistochemical staining revealed that MAIT cells in the gut mucosa of HIV-1 infected patients exhibited a strong active gasdermin-D(GSDMD, marker of pyroptosis) signal near the cavity side, suggesting that these MAIT cells underwent active pyroptosis in the colorectal mucosa. Increased levels of the proinflammatory cytokines interleukin-12(IL-12) and IL-18 were observed in HIV-1 infected patients. In addition, activated MAIT cells exhibited an increased pyroptotic phenotype after being triggered by HIV-1 virions, T-cell receptor signals, IL-12 plus IL-18, and combinations of these factors, in vitro.Conclusions: Activation-induced MAIT cell pyroptosis contributes to the loss of MAIT cells in HIV-1 infected patients,which could potentiate disease progression and poor immune reconstitution.展开更多
Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells;for IgG production th...Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells;for IgG production through the same process, however, a second signal is required. Previous studies have reported that invariant natural killer T (iNKT) cells may be responsible for the second signal involved in IgG production. In the present study, we addressed whether human iNKT cells could participate in the production of Ig against TI-2 Ag in vitro. Two major distinct subsets of human iNKT cells, CD4<sup>+</sup> CD8β<sup>-</sup> (CD4) and CD4<sup>-</sup> CD8β<sup>-</sup> [double negative (DN)] cells, were generated from peripheral blood monocytes from a healthy volunteer. BCR engagement, triggered by anti-IgM antibody stimulation, examined here as a model of BCR engagement triggered by TI-2 Ag, induced abundant IgM production by B cells. Both CD4 and DN iNKT cells reduced IgM production and conversely enhanced IgG production in a dose-dependent manner. In addition, IgG production by CD19<sup>+</sup>CD27<sup>-</sup> (naïve) and CD19<sup>+</sup>CD27<sup>+</sup> (memory) B cells was predominantly promoted by DNiNKT cells rather than CD4 iNKT cells;nevertheless, IgM production by both B cell subsets was similarly reduced by either subset of iNKT cells. These results suggest that the DN iNKT subsets may preferentially promote Ig class switching by B cells upon stimulation with TI-2 Ag.展开更多
AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetu...AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetuximab.METHODS: Forty-one KRAS wt mC RC patients,treated with cetuximab and irinotecan-based chemotherapy in Ⅱ and Ⅲ lines were analyzed. Genotyping of single nucleotide polymorphism(SNP)s in the FCGR2A,FCGR3A and in the 3' untranslated regions of KRAS and mutational analysis for KRAS,BRAF and NRAS genes was determined either by sequencing or allelic discrimination assays. Enriched NK cells were obtained from lymphoprepperipheral blood mononuclear cell and iN KT cells were defined by co-expression of CD3,TCRVα24,TCRVβ11. ADCC was evaluated as ex vivo NK-dependent activity,measuring lactate dehydrogenase release.RESULTS: At basal,mCRC patients performing ADCC activity above the median level(71%) showed an improved overall survival(OS) compared to patients with ADCC below(median 16 vs 8 mo;P=0.026). We did not find any significant correlation of iN KT cells with OS(P=0.19),albeit we observed a trend to a longer survival after 10 mo in patients with iN KT above median basal level(0.382 cells/microliter). Correlation of OS and progression-free survival(PFS) with interesting SNPs involved in ADCC ability revealed not to be significant. Patients carrying alleles both with A in FCGR2 A and TT in FCGR3A presented a trend of longer PFS(median 9 vs 5 mo;P=0.064). Chemotherapy impacted both iN KT cells and ADCC activity. Their prognostic values get lost when we analysed them after 2 and 4 mo of treatment.CONCLUSION: Our results suggest a link between iN KT cells,basal ADCC activity,genotypes in FCGR2A and FCGR3A,and efficacy of cetuximab in KRAS wt mC RC patients.展开更多
黏膜相关恒定T细胞(mucosal-associated invariant T cells,MAIT细胞)是一类进化保守的固有样淋巴细胞,通过主要组织相容性复合体Ⅰ类样蛋白识别抗原,分泌多种细胞因子,产生细胞毒性,发挥免疫学效应。MAIT细胞作为具有适应性免疫功能特...黏膜相关恒定T细胞(mucosal-associated invariant T cells,MAIT细胞)是一类进化保守的固有样淋巴细胞,通过主要组织相容性复合体Ⅰ类样蛋白识别抗原,分泌多种细胞因子,产生细胞毒性,发挥免疫学效应。MAIT细胞作为具有适应性免疫功能特点的固有免疫细胞,参与了多种感染性疾病的发生发展,有望成为潜在的免疫治疗靶点。展开更多
基金Supported by National Natural Science Foundation of China,No.81600449Nantong Science and Technology Bureau,No.MS22018007,No.MSZ18130,and No.JCZ18036+2 种基金Six Peak Talents in Jiangsu Province,No.YY-177Project of Jiangsu Province Youth Medical Talent Development,No.QNRC2016400and Project of Nantong Youth Medical Talent Development,No.05.
文摘BACKGROUND Liver failure has high mortality and poor prognosis,and establishing new reliable markers for predicting its prognosis is necessary.Mucosal-associated invariant T(MAIT)cells are a novel population of innate-like lymphocytes involved in inflammatory liver disease,and their potential role in liver failure remains unclear.AIM To investigate alteration of circulating MAIT cells and assess its prognostic value in patients with hepatitis B virus(HBV)-related liver failure.METHODS We recruited 55 patients with HBV-related liver failure,48 patients with chronic hepatitis B and 40 healthy controls(HCs)from Nantong Third People’s Hospital Affiliated to Nantong University.Peripheral blood mononuclear cells were isolated,and the percentage and number of circulating MAIT cells were detected by flow cytometry.Plasma levels of interleukin(IL)-7,IL-12p70,IL-18 and interferon-αwere measured by Luminex assay.RESULTS Circulating MAIT cells were significantly decreased in HBV-related liver failure patients(percentage:2.00±1.22 vs 5.19±1.27%,P<0.0001;number:5.47±4.93 vs 84.43±19.59,P<0.0001)compared with HCs.More importantly,there was a significant reduction of MAIT cells in patients with middle/late-stage compared with early-stage liver failure.Circulating MAIT cells partially recovered after disease improvement,both in percentage(4.01±1.21 vs 2.04±0.95%,P<0.0001)and in cell count(17.24±8.56 vs 7.41±4.99,P<0.0001).The proportion(2.29±1.01 vs 1.58±1.38%,P<0.05)and number(7.30±5.70 vs 2.94±1.47,P<0.001)of circulating MAIT cells were significantly higher in the survival group than in the dead/liver transplantation group,and the Kaplan–Meier curve showed that lower expression of circulating MAIT cells(both percentage and cell count)predicted poor overall survival(P<0.01).Also,the levels of IL-12(20.26±5.42 pg/mL vs 17.76±2.79 pg/mL,P=0.01)and IL-18(1470.05±1525.38 pg/mL vs 362.99±109.64 pg/mL,P<0.0001)were dramatically increased in HBV-related liver failure patients compared with HCs.CONCLUSION Circulating MAIT cells may play an important role in the process of HBV-related liver failure and can be an important prognostic marker.
文摘Mice have frequently been used to model human diseases involving immune dysregulation such as autoimmune and inflammatory diseases.These models help elucidatethe mechanisms underlying the disease and in the development of novel therapies.However,if mice are deficient in certain cells and/or effectors associated with human diseases,how can their functions be investigated in this species?Mucosal-associated invariant T(MAIT)cells,a novel innate-like T cell family member,are a good example.MAIT cells are abundant in humans but scarce in laboratory mice.MAIT cells harbor an invariant T cell receptor and recognize nonpeptidic antigens vitamin B2metabolites from bacteria and yeasts.Recent studies have shown that MAIT cells play a pivotal role in human diseases such as bacterial infections and autoimmune and inflammatory diseases.MAIT cells possess granulysin,a human-specific effector molecule,but granulysin and its homologue are absent in mice.Furthermore,MAIT cells show poor proliferation in vitro.To overcome these problems and further our knowledge of MAIT cells,we have established a method to expand MAIT cells via induced pluripotent stem cells(iP SCs).In this review,we describe recent advances in the field of MAIT cell research and our approach for human disease modeling with iP SCderived MAIT cells.
文摘Mucosal-associated invariant T(MAIT)cells have been described in liver and nonliver diseases,and they have been ascribed antimicrobial,immune regulatory,protective,and pathogenic roles.The goals of this review are to describe their biological properties,indicate their involvement in chronic liver disease,and encourage investigations that clarify their actions and therapeutic implications.English abstracts were identified in PubMed by multiple search terms,and bibliographies were developed.MAIT cells are activated by restricted non-peptides of limited diversity and by multiple inflammatory cytokines.Diverse pro-inflammatory,anti-inflammatory,and immune regulatory cytokines are released;infected cells are eliminated;and memory cells emerge.Circulating MAIT cells are hyper-activated,immune exhausted,dysfunctional,and depleted in chronic liver disease.This phenotype lacks disease-specificity,and it does not predict the biological effects.MAIT cells have presumed protective actions in chronic viral hepatitis,alcoholic hepatitis,non-alcoholic fatty liver disease,primary sclerosing cholangitis,and decompensated cirrhosis.They have pathogenic and pro-fibrotic actions in autoimmune hepatitis and mixed actions in primary biliary cholangitis.Local factors in the hepatic microenvironment(cytokines,bile acids,gut-derived bacterial antigens,and metabolic by-products)may modulate their response in individual diseases.Investigational manipulations of function are warranted to establish an association with disease severity and outcome.In conclusion,MAIT cells constitute a disease-nonspecific,immune response to chronic liver inflammation and infection.Their pathological role has been deduced from their deficiencies during active liver disease,and future investigations must clarify this role,link it to outcome,and explore therapeutic interventions.
文摘Opportunistic bacteria in apical periodontitis (AP) may pose a risk for systemic dissemination.Mucosal-associated invariant T (MAIT) cells are innate-like T cells with a broad and potent antimicrobial activity important for gut mucosal integrity.It was recently shown that MAIT cells are present in the oral mucosal tissue,but the involvement of MAIT cells in AP is unknown.Here,comparison of surgically resected AP and gingival tissues demonstrated that AP tissues express significantly higher levels of Vα7.2-Jα33,Vα7.2- Jα20,Vα7.2-Jα12,Cα and tumour necrosis factor (TNF),interferon (IFN)-γ and interleukin (IL)-17A transcripts,resembling a MAIT cell signature.Moreover,in AP tissues the MR1-restricted MAIT cells positive for MR1–5-OP-RU tetramer staining appeared to be of similar levels as in peripheral blood but consisted mainly of CD4^+ subset.Unlike gingival tissues,the AP microbiome was quantitatively impacted by factors like fistula and high patient age and had a prominent riboflavin-expressing bacterial feature.When merged in an integrated view,the examined immune and microbiome data in the sparse partial least squares discriminant analysis could identify bacterial relative abundances that negatively correlated with Vα7.2-Jα33,Cα,and IL-17A transcript expressions in AP,implying that MAIT cells could play a role in the local defence at the oral tissue barrier.In conclusion,we describe the presence of MAIT cells at the oral site where translocation of oral microbiota could take place.These findings have implications for understanding the immune sensing of polymicrobial-related oral diseases.
基金supported by the Peking University Clinical Scientist Program Special(BMU2019LCKXJ013)the National Natural Science Foundation Innovation Research Group Project(81721002)+2 种基金the Sanming Project of Medicine Project in Shenzhen(SZSM201612014)the Yunnan Applied Basic Research Projects-Union Foundation by Yunnan Provincial Department of Science and Technology and Kunming Medical University(202001AY070001-154)the Scientific Research Fund of Education Department of Yunnan Province(2021J0297)。
文摘Background: Mucosal-associated invariant T(MAIT) cells are systemically depleted in human immunodeficiency virus type 1(HIV-1) infected patients and are not replenished even after successful combined antiretroviral therapy(cART).This study aimed to identify the mechanism underlying MAIT cell depletion.Methods: In the present study, we applied flow cytometry, single-cell RNA sequencing and immunohistochemical staining to evaluate the characteristics of pyroptotic MAIT cells in a total of 127 HIV-1 infected individuals, including 69 treatment-naive patients, 28 complete responders, 15 immunological non-responders, and 15 elite controllers, at the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.Results: Single-cell transcriptomic profiles revealed that circulating MAIT cells from HIV-1 infected subjects were highly activated, with upregulation of pyroptosis-related genes. Further analysis revealed that increased frequencies of pyroptotic MAIT cells correlated with markers of systemic T-cell activation, microbial translocation, and intestinal damage in cART-naive patients and poor CD4+ T-cell recovery in long-term cART patients. Immunohistochemical staining revealed that MAIT cells in the gut mucosa of HIV-1 infected patients exhibited a strong active gasdermin-D(GSDMD, marker of pyroptosis) signal near the cavity side, suggesting that these MAIT cells underwent active pyroptosis in the colorectal mucosa. Increased levels of the proinflammatory cytokines interleukin-12(IL-12) and IL-18 were observed in HIV-1 infected patients. In addition, activated MAIT cells exhibited an increased pyroptotic phenotype after being triggered by HIV-1 virions, T-cell receptor signals, IL-12 plus IL-18, and combinations of these factors, in vitro.Conclusions: Activation-induced MAIT cell pyroptosis contributes to the loss of MAIT cells in HIV-1 infected patients,which could potentiate disease progression and poor immune reconstitution.
文摘Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells;for IgG production through the same process, however, a second signal is required. Previous studies have reported that invariant natural killer T (iNKT) cells may be responsible for the second signal involved in IgG production. In the present study, we addressed whether human iNKT cells could participate in the production of Ig against TI-2 Ag in vitro. Two major distinct subsets of human iNKT cells, CD4<sup>+</sup> CD8β<sup>-</sup> (CD4) and CD4<sup>-</sup> CD8β<sup>-</sup> [double negative (DN)] cells, were generated from peripheral blood monocytes from a healthy volunteer. BCR engagement, triggered by anti-IgM antibody stimulation, examined here as a model of BCR engagement triggered by TI-2 Ag, induced abundant IgM production by B cells. Both CD4 and DN iNKT cells reduced IgM production and conversely enhanced IgG production in a dose-dependent manner. In addition, IgG production by CD19<sup>+</sup>CD27<sup>-</sup> (naïve) and CD19<sup>+</sup>CD27<sup>+</sup> (memory) B cells was predominantly promoted by DNiNKT cells rather than CD4 iNKT cells;nevertheless, IgM production by both B cell subsets was similarly reduced by either subset of iNKT cells. These results suggest that the DN iNKT subsets may preferentially promote Ig class switching by B cells upon stimulation with TI-2 Ag.
基金the Fondazione Veronesi that granted Daniela Vivenza and Martino Monteverde with PostDoctoral Fellowship Veronesithe Fondazione Cassa Risparmio of Cuneo for partially supporting the study
文摘AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetuximab.METHODS: Forty-one KRAS wt mC RC patients,treated with cetuximab and irinotecan-based chemotherapy in Ⅱ and Ⅲ lines were analyzed. Genotyping of single nucleotide polymorphism(SNP)s in the FCGR2A,FCGR3A and in the 3' untranslated regions of KRAS and mutational analysis for KRAS,BRAF and NRAS genes was determined either by sequencing or allelic discrimination assays. Enriched NK cells were obtained from lymphoprepperipheral blood mononuclear cell and iN KT cells were defined by co-expression of CD3,TCRVα24,TCRVβ11. ADCC was evaluated as ex vivo NK-dependent activity,measuring lactate dehydrogenase release.RESULTS: At basal,mCRC patients performing ADCC activity above the median level(71%) showed an improved overall survival(OS) compared to patients with ADCC below(median 16 vs 8 mo;P=0.026). We did not find any significant correlation of iN KT cells with OS(P=0.19),albeit we observed a trend to a longer survival after 10 mo in patients with iN KT above median basal level(0.382 cells/microliter). Correlation of OS and progression-free survival(PFS) with interesting SNPs involved in ADCC ability revealed not to be significant. Patients carrying alleles both with A in FCGR2 A and TT in FCGR3A presented a trend of longer PFS(median 9 vs 5 mo;P=0.064). Chemotherapy impacted both iN KT cells and ADCC activity. Their prognostic values get lost when we analysed them after 2 and 4 mo of treatment.CONCLUSION: Our results suggest a link between iN KT cells,basal ADCC activity,genotypes in FCGR2A and FCGR3A,and efficacy of cetuximab in KRAS wt mC RC patients.
文摘黏膜相关恒定T细胞(mucosal-associated invariant T cells,MAIT细胞)是一类进化保守的固有样淋巴细胞,通过主要组织相容性复合体Ⅰ类样蛋白识别抗原,分泌多种细胞因子,产生细胞毒性,发挥免疫学效应。MAIT细胞作为具有适应性免疫功能特点的固有免疫细胞,参与了多种感染性疾病的发生发展,有望成为潜在的免疫治疗靶点。
