Tumor-infiltrating CD39+ γδTregs are novel immunosuppressive T cells in human colorectal cancer

• Published in: Oncoimmunology 2017-02, Vol.6 (2), p.e1277305-e1277305
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adenosine; CD39; cd39+ γδtregs; human CRC; Original Research; tumor-derived TGF-β1; γδTregs
• ISSN: 2162-4011; 2162-402X
• DOI: 10.1080/2162402X.2016.1277305

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.