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

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

Oncoimmunology. 2017;6(2):e1277305

Authors: Hu G, Wu P, Cheng P, Zhang Z, Wang Z, Yu X, Shao X, Wu D, Ye J, Zhang T, Wang X, Qiu F, Yan J, Huang J

Abstract
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.

PMID: 28344891 [PubMed - in process]

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