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Immunity. 2014 May 15;40(5):785-800. doi: 10.1016/j.immuni.2014.03.013. Epub 2014 May 8.

γδT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer.

Author information

1
Cancer Institute (Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education; Provincial Key Laboratory of Molecular Biology in Medical Sciences), Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China; Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
2
Cancer Institute (Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education; Provincial Key Laboratory of Molecular Biology in Medical Sciences), Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China; Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
3
Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
4
Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
5
Cancer Institute (Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education; Provincial Key Laboratory of Molecular Biology in Medical Sciences), Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
6
Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
7
Cancer Institute (Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education; Provincial Key Laboratory of Molecular Biology in Medical Sciences), Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China; Department of Radiation Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
8
Department of Clinical Laboratory, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
9
Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
10
Department of Medicine and Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA. Electronic address: jun.yan@louisville.edu.
11
Cancer Institute (Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education; Provincial Key Laboratory of Molecular Biology in Medical Sciences), Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China; Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China. Electronic address: drhuangjian@zju.edu.cn.

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.

PMID:
24816404
PMCID:
PMC4716654
DOI:
10.1016/j.immuni.2014.03.013
[Indexed for MEDLINE]
Free PMC Article

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