CD226 has been reported to participate in the rescue of CD8^(+)T cell dysfunction.In this study,we aimed to assess the prognostic value of CD226 in tumor-infiltrating lymphocytes(TILs)derived from colorectal cancer(CRC...CD226 has been reported to participate in the rescue of CD8^(+)T cell dysfunction.In this study,we aimed to assess the prognostic value of CD226 in tumor-infiltrating lymphocytes(TILs)derived from colorectal cancer(CRC)liver metastases treated with chemotherapy and radical surgery.TILs from 43 metastases were isolated and analyzed ex vivo usingflow cytometry.CD155 and CD3 levels in the tumor microenvironment were assessed by immunohistochemistry.Exploration and validation of biological processes highlighted in this study were performed by bioinformatics analysis of bulk RNA-seq results for 28 CRC liver metastases pretreated with chemotherapy as well as public gene expression datasets.CD226 expression contributes to the definition of the immune context in CRC liver metastases and primary tumors.CD226 on CD8^(+)T cells was not specifically coexpressed with other immune checkpoints,such as PD1,TIGIT,and TIM3,in liver metastases.Multivariate Cox regression analysis revealed CD226 expression on CD8^(+)T cells to be an independent prognostic factor(p=0.003),along with CD3 density at invasion margins(p=0.003)and TIGIT expression on CD4^(+)T cells(p=0.019).CD155 was not associated with the prognostic value of CD226.Gene expression analysis in a validation dataset confirmed the prognostic value of CD226 in CRC liver metastases but not in primary tumors.Downregulation of CD226 on CD8^(+)TILs in the liver microenvironment was restored by IL15 treatment.Overall,CD226 expression on liver metastasis-infiltrating CD8^(+)T cells selectively contributes to immune surveillance of CRC liver metastases and has prognostic value for patients undergoing radical surgery.展开更多
文摘既往腹膜表面肿瘤学科的培训常通过医师的个人自学实现,鉴于目前这一学科的发展,对该领域专家的需求越来越大,因此有必要形成组织化的教育和培训方式。在欧洲外科肿瘤学会(ESSO)和国际腹膜表面恶性肿瘤学会(Peritoneal Surface Oncology Group International,PSOGI)的共同努力下,欧洲腹膜表面肿瘤学院(ESPSO)于2014年成立。该组织基于导师制的腹膜表面肿瘤学培训项目,已获得欧洲认证。自该项目成立年至2021年7月14日,共有42名外科医生从该培训项目毕业,其中大多数来自欧洲,也有部分非欧洲的毕业生,这使得该项目具有全球影响力。目前,已有35名候选学员已在欧洲和非欧洲培训中心完成注册。鉴于当前培训的成功,该项目正在加速发展,目前不断有新的教员加入以及新的培训活动开展。欧洲腹膜表面肿瘤学学院成功建立了一个结构化的基于导师制的培训项目,并获得了专业认证。得益于来自全球的大量毕业生和候选学员,使该项目获得了预期的声望,满足了学员的需求,并为本培训项目下一步计划的实施提供了保障。本文主要介绍此培训项目方案。
文摘CD226 has been reported to participate in the rescue of CD8^(+)T cell dysfunction.In this study,we aimed to assess the prognostic value of CD226 in tumor-infiltrating lymphocytes(TILs)derived from colorectal cancer(CRC)liver metastases treated with chemotherapy and radical surgery.TILs from 43 metastases were isolated and analyzed ex vivo usingflow cytometry.CD155 and CD3 levels in the tumor microenvironment were assessed by immunohistochemistry.Exploration and validation of biological processes highlighted in this study were performed by bioinformatics analysis of bulk RNA-seq results for 28 CRC liver metastases pretreated with chemotherapy as well as public gene expression datasets.CD226 expression contributes to the definition of the immune context in CRC liver metastases and primary tumors.CD226 on CD8^(+)T cells was not specifically coexpressed with other immune checkpoints,such as PD1,TIGIT,and TIM3,in liver metastases.Multivariate Cox regression analysis revealed CD226 expression on CD8^(+)T cells to be an independent prognostic factor(p=0.003),along with CD3 density at invasion margins(p=0.003)and TIGIT expression on CD4^(+)T cells(p=0.019).CD155 was not associated with the prognostic value of CD226.Gene expression analysis in a validation dataset confirmed the prognostic value of CD226 in CRC liver metastases but not in primary tumors.Downregulation of CD226 on CD8^(+)TILs in the liver microenvironment was restored by IL15 treatment.Overall,CD226 expression on liver metastasis-infiltrating CD8^(+)T cells selectively contributes to immune surveillance of CRC liver metastases and has prognostic value for patients undergoing radical surgery.
