| Literature DB >> 24816404 |
Pin Wu1, Dang Wu1, Chao Ni1, Jun Ye2, Wuzhen Chen3, Guoming Hu1, Zhen Wang1, Changrong Wang4, Zhigang Zhang3, Wenjie Xia3, Zhigang Chen1, Ke Wang3, Tao Zhang5, Jinghong Xu4, Yuehua Han6, Ting Zhang7, Xianguo Wu8, Jianwei Wang3, Weihua Gong9, Shu Zheng5, Fuming Qiu1, Jun Yan10, Jian Huang11.
Abstract
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 γδT (γδT17) 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 γδT17 polarization in human tumors. Activated inf-DCs induced γδT17 cells to secrete IL-8, tumor necrosis factor alpha, and GM-CSF with a concomitant accumulation of immunosuppressive PMN-MDSCs in the tumor. Importantly, γδT17 cell infiltration positively correlated with tumor stages and other clinicopathological features. Our study uncovers an inf-DC-γδT17-PMN-MDSC regulatory axis in human CRC that correlates MDSC-meditated immunosuppression with tumor-elicited inflammation. These findings suggest that γδT17 cells might be key players in human CRC progression and have the potential for treatment or prognosis prediction.Entities:
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Year: 2014 PMID： 24816404 PMCID： PMC4716654 DOI： 10.1016/j.immuni.2014.03.013
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745