Hu Guoming, Wu Pin, Cheng Pu, Zhang Zhigang, Wang Zhen, Yu Xiuyan, Shao Xuan, Wu Dang, Ye Jun, Zhang Tao, Wang Xiaochen, Qiu Fuming, Yan Jun, Huang Jian
Cancer Institute, Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China; Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Cancer Institute, Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China; Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Oncoimmunology. 2017 Jan 6;6(2):e1277305. doi: 10.1080/2162402X.2016.1277305. eCollection 2017.
Tumor microenvironment (TME) promotes immune suppression through recruiting and expanding suppressive immune cells such as regulatory T cells (Tregs) to facilitate cancer progression. In this study, we identify a novel CD39 γδTreg in human colorectal cancer (CRC). CD39 γδTregs are the predominant regulatory T cells and have more potent immunosuppressive activity than CD4 or CD8 Tregs via the adenosine-mediated pathway but independent of TGF-β or IL-10. They also secrete cytokines including IL-17A and GM-CSF, which may chemoattract myeloid-derived suppressive cells (MDSCs), thus establishing an immunosuppressive network. We further demonstrate that tumor-derived TGF-β1 induces CD39 γδT cells from paired normal colon tissues to produce more adenosine and become potent immunosuppressive T cells. Moreover, CD39 γδTreg infiltration is positively correlated with TNM stage and other unfavorable clinicopathological features, implicating that CD39 γδTregs are one of the key players in establishment of immunosuppressive TME in human CRC that may be critical for tumor immunotherapy.
肿瘤微环境（TME）通过招募和扩增诸如调节性T细胞（Tregs）等抑制性免疫细胞来促进免疫抑制，从而推动癌症进展。在本研究中，我们在人类结直肠癌（CRC）中鉴定出一种新型的CD39 γδTreg。CD39 γδTregs是主要的调节性T细胞，通过腺苷介导的途径比CD4或CD8 Tregs具有更强的免疫抑制活性，但不依赖于转化生长因子-β（TGF-β）或白细胞介素-10（IL-10）。它们还分泌包括白细胞介素-17A（IL-17A）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）在内的细胞因子，这可能趋化骨髓来源的抑制性细胞（MDSCs），从而建立一个免疫抑制网络。我们进一步证明，肿瘤来源的TGF-β1可诱导来自配对正常结肠组织的CD39 γδT细胞产生更多腺苷并成为强效免疫抑制性T细胞。此外，CD39 γδTreg浸润与TNM分期及其他不良临床病理特征呈正相关，这表明CD39 γδTregs是人类CRC中建立免疫抑制性TME的关键参与者之一，这可能对肿瘤免疫治疗至关重要。
