γδT17 Cells Promote the Accumulation and Expansion of Myeloid-Derived Suppressor Cells in Human Colorectal Cancer

Development of cancer has been linked to chronic inflammation, particularly via interleukin-23 (IL-23) and IL-17 signaling pathways. However, the cellular source of IL-17 and underlying mechanisms by which IL-17-producing cells promote human colorectal cancer (CRC) remain poorly defined. Here, we demonstrate that innate gamma delta T (gamma delta T17) cells are the major cellular source of IL-17 in human CRC. Microbial products elicited by tumorous epithelial barrier disruption correlated with inflammatory dendritic cell (inf-DC) accumulation and gamma delta T17 polarization in human tumors. Activated inf-DCs induced gamma delta T17 cells to secrete IL-8, tumor necrosis factor alpha, and GM-CSF with a concomitant accumulation of immunosuppressive PMN-MDSCs in the tumor. Importantly, gamma delta T17 cell infiltration positively correlated with tumor stages and other clinicopathological features. Our study uncovers an inf-DC-gamma delta T17-PMN-MDSC regulatory axis in human CRC that correlates MDSC-meditated immunosuppression with tumorelicited inflammation. These findings suggest that gamma delta T17 cells might be key players in human CRC progression and have the potential for treatment or prognosis prediction.