Background:This study was designed to investigate the feasibility of tumor-infiltrating immune cells with different phenotypic characteristics for predicting short-term clinical responses in patients with locally adva...Background:This study was designed to investigate the feasibility of tumor-infiltrating immune cells with different phenotypic characteristics for predicting short-term clinical responses in patients with locally advanced cervical cancer(LACC).Methods:Thirty-four patients who received concurrent chemoradiotherapy and twenty-one patients who merely underwent radiotherapy were enrolled in this study.We retrospectively analyzed the T cell markers(i.e.,CD3,CD4,CD8),memory markers(i.e.,CD45,CCR7),and differentiation markers(i.e.,CD27)in the peripheral blood and tumor tissues of patients with LACC before treatment based on flow cytometry.We also analyzed the relationship of T cell subsets between peripheral blood and tumor tissues,and their correlation with complete response or partial response.Results:The percentage of central memory CD8^(+)TCM(CD8^(+)CD45RA^(−)CD27^(+)CCR7^(+))cells in LACC patients was significantly lower than that of the control group.The percentage of CD8^(+)TN in the peripheral blood of LACC patients was significantly higher than that of tumor tissues.CD8^(+)TEM in the peripheral blood was significantly lower than that of tumor tissues.The percentage of CD8^(+)TN and CD8^(+)TCM in human papillomavirus(HPV)positive samples was significantly higher than that of HPV-negative samples.Similarly,the percentage of CD8^(+)TCM in tumor tissues was significantly higher in cancer tissue samples with lymph nodes compared with those without.Conclusion:A higher proportion of CD4^(+)TCM and a lower proportion of CD8^(+)TN in the tumor microenvironment of LACC may contribute to the therapy response prediction.展开更多
Solid organ transplant(SOT)recipients receive immunosuppressive drugs(ISDs)and are susceptible to developing severe COVID-19.Here,we analyze the Spike-specific T-cell response after 3 doses of mRNA vaccine in a group ...Solid organ transplant(SOT)recipients receive immunosuppressive drugs(ISDs)and are susceptible to developing severe COVID-19.Here,we analyze the Spike-specific T-cell response after 3 doses of mRNA vaccine in a group of SOT patients(n=136)treated with different ISDs.We demonstrate that a combination of a calcineurin inhibitor(CNI),mycophenolate mofetil(MMF),and prednisone(Pred)treatment regimen strongly suppressed the mRNA vaccine-induced Spike-specific cellular response.Such defects have clinical consequences because the magnitude of vaccine-induced Spike-specific T cells was directly proportional to the ability of SOT patients to rapidly clear SARS-CoV-2 after breakthrough infection.To then compensate for the T-cell defects induced by immunosuppressive treatment and to develop an alternative therapeutic strategy for SOT patients,we describe production of 6 distinct SARS-CoV-2 epitope-specific ISD-resistant T-cell receptor(TCR)-T cells engineered using the mRNA electroporation method with reactivity minimally affected by mutations occurring in Beta,Delta,Gamma,and Omicron variants.This strategy with transient expression characteristics marks an improvement in the immunotherapeutic field and provides an attractive and novel therapeutic possibility for immunosuppressed COVID-19 patients.展开更多
In this review,we will highlight the importance of cancer germline antigen-specific cytotoxic CD8^(+) T lymphocytes(CTL)and the factors affecting antitumor CTL responses.In light of cancer immunotherapy,we will emphas...In this review,we will highlight the importance of cancer germline antigen-specific cytotoxic CD8^(+) T lymphocytes(CTL)and the factors affecting antitumor CTL responses.In light of cancer immunotherapy,we will emphasis the need to further understand the features,characteristics,and actions of modulatory receptors of human cancer germline-specific CTLs,in order to determine the optimal conditions for antitumor CTL responses.展开更多
基金the Project of the Central Government Guiding Local Science and Technology under Grant Number ZYYD2022B18the Institutional Ethics Committee of Affiliated Cancer Hospital of Xinjiang Medical University(No.K-2019001).
文摘Background:This study was designed to investigate the feasibility of tumor-infiltrating immune cells with different phenotypic characteristics for predicting short-term clinical responses in patients with locally advanced cervical cancer(LACC).Methods:Thirty-four patients who received concurrent chemoradiotherapy and twenty-one patients who merely underwent radiotherapy were enrolled in this study.We retrospectively analyzed the T cell markers(i.e.,CD3,CD4,CD8),memory markers(i.e.,CD45,CCR7),and differentiation markers(i.e.,CD27)in the peripheral blood and tumor tissues of patients with LACC before treatment based on flow cytometry.We also analyzed the relationship of T cell subsets between peripheral blood and tumor tissues,and their correlation with complete response or partial response.Results:The percentage of central memory CD8^(+)TCM(CD8^(+)CD45RA^(−)CD27^(+)CCR7^(+))cells in LACC patients was significantly lower than that of the control group.The percentage of CD8^(+)TN in the peripheral blood of LACC patients was significantly higher than that of tumor tissues.CD8^(+)TEM in the peripheral blood was significantly lower than that of tumor tissues.The percentage of CD8^(+)TN and CD8^(+)TCM in human papillomavirus(HPV)positive samples was significantly higher than that of HPV-negative samples.Similarly,the percentage of CD8^(+)TCM in tumor tissues was significantly higher in cancer tissue samples with lymph nodes compared with those without.Conclusion:A higher proportion of CD4^(+)TCM and a lower proportion of CD8^(+)TN in the tumor microenvironment of LACC may contribute to the therapy response prediction.
基金We would like to acknowledge the contribution of the Singapore National University Centre for Organ Transplantation team members who helped recruit patients:AV,AL,and WKK.We thank all voluntary blood donors for their donations.We would like to thank the members of AB’s lab for their insights and critique.Finally,we would also like to thank Dr.Yongxu Lu and Prof.Geoffrey L.Smith from the Department of Pathology,University of Cambridge,U.K.,for supplying the vaccinia virus-expressing Spike and Nucleocapsid proteins.This study was supported by research funding from the Singapore Ministry of Health’s National Medical Research Council MOH-000019(MOH-StaR17Nov-001)to Antonio BertolettiPart of this work was also supported by the A*ccelerate GAP-funded project(ACCL/19-GAP064-R20H-H)from the Agency of Science+1 种基金Technology and Research(A*STAR),the Singapore National Medical Research Council COVID-19 Research Fund(COVID19RF-011)a Start-up University Grant from the Ministry of Education(Singapore)to Laurent Renia.YSG was supported by a Career Development Fund award by A*STAR(SC35/22-805100).
文摘Solid organ transplant(SOT)recipients receive immunosuppressive drugs(ISDs)and are susceptible to developing severe COVID-19.Here,we analyze the Spike-specific T-cell response after 3 doses of mRNA vaccine in a group of SOT patients(n=136)treated with different ISDs.We demonstrate that a combination of a calcineurin inhibitor(CNI),mycophenolate mofetil(MMF),and prednisone(Pred)treatment regimen strongly suppressed the mRNA vaccine-induced Spike-specific cellular response.Such defects have clinical consequences because the magnitude of vaccine-induced Spike-specific T cells was directly proportional to the ability of SOT patients to rapidly clear SARS-CoV-2 after breakthrough infection.To then compensate for the T-cell defects induced by immunosuppressive treatment and to develop an alternative therapeutic strategy for SOT patients,we describe production of 6 distinct SARS-CoV-2 epitope-specific ISD-resistant T-cell receptor(TCR)-T cells engineered using the mRNA electroporation method with reactivity minimally affected by mutations occurring in Beta,Delta,Gamma,and Omicron variants.This strategy with transient expression characteristics marks an improvement in the immunotherapeutic field and provides an attractive and novel therapeutic possibility for immunosuppressed COVID-19 patients.
基金This work was supported by Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS),China(grant number:2018-I2M-2-002)MRC Human Immunology Unit Core and Nuffield Department of Medicine,Oxford University.Illustrations were created with BioRender(Biorender.com)。
文摘In this review,we will highlight the importance of cancer germline antigen-specific cytotoxic CD8^(+) T lymphocytes(CTL)and the factors affecting antitumor CTL responses.In light of cancer immunotherapy,we will emphasis the need to further understand the features,characteristics,and actions of modulatory receptors of human cancer germline-specific CTLs,in order to determine the optimal conditions for antitumor CTL responses.