title: γδT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer.
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.
authors.affiliation: 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.
authors.forename: Pin
authors.initials: P
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Dang
authors.initials: D
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Chao
authors.initials: C
authors.lastname: Ni
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Wuzhen
authors.initials: W
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Guoming
authors.initials: G
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Changrong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Xia
authors.affiliation: 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.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Xianguo
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Gong
authors.affiliation: 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.
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: Fuming
authors.initials: F
authors.lastname: Qiu
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
mesh_terms: D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D016209:Interleukin-8 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D016209:Interleukin-8; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor