Tumor-infiltrating CD39Tregs are novel immunosuppressive T cells in human colorectal cancer.

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.