Human hepatocellular carcinoma-infiltrating CD4+CD69+Foxp3-regulatory T cell suppresses T cell response via membrane-bound TGF-β1
作者单位：National Key Laboratory of Medical Immunology & Institute of Immunology Second Military Medical University
会议名称：《第十四届全国肿瘤生物治疗大会》
会议日期：2015年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：regulatory T cells CD69 transforming growth factor-β1 tumor immune escape hepatocellular carcinoma
摘 要：Tumors can recruit, induce and expand regulatory T cells(Tregs) to suppress anti-tumor immune responses for survival and progression. The complicated tumor-related Treg subsets and their functional mechanisms are not fully addressed yet. We have previously identified a novel CD4+CD69+CD25-Foxp3- Treg subset in tumor-bearing mice, which suppresses CD4 T cell response via membrane-bound TGF-β1(mT GF-β1) and then promotes tumor progression. In hepatocellular carcinoma patients, here we identified tumor-infiltrating human CD4+CD69+ Tregs which represent 7.2% of tumor-infiltrating CD4 T cells, significantly higher than conventional CD4+CD25+Foxp3+ Tregs. They expressed mT GF-β1, PD-1 and CTLA-4, but not CD25 or Foxp3, only produced a little IL-10 and TGF-β1. More importantly, they significantly suppressed CD4 T cell response via mT GF-β1 in vitro. Furthermore, the percentage of these CD4+CD69+ Tregs in tumor tissue was significantly correlated with tumor progression, with more pronounced at late stage of cancer patients. Thus we have identified a tumor-induced new population of human CD4+CD69+ Tregs in cancer patients, with phenotype of CD25-Foxp3-mT GF-β1+CTLA-4+PD-1+, and these Tregs can suppress anti-tumor immune response via mT GF-β1. Our results not only enrich the family of Treg subsets, providing new mechanistic insight to tumor-induced immune suppression in human, but also suggest a potential target for cancer immunotherapy.