1. CD8(+) T cells that produce interleukin-17 regulate myeloid-derived suppressor cells and are associated with survival time of patients with gastric cancer
- Author
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Na Li, Liu Sheng Peng, Quan Ming Zou, Yuan Zhuang, Kai Yun Liu, Yong-liang Zhao, Yan Shi, Gang Guo, Xiao-fei Liu, Weijun Zhang, Xu Hu Mao, Pei‑Wu Yu, Jin Yu Zhang, Hao Zeng, Ping Luo, Weisan Chen, Wen De Tong, Tao Liu, Shu Yu, Ken C Pang, Bin Tang, Yun Shi, and Dong–Shui Lu
- Subjects
Male ,Receptors, CXCR4 ,Interleukin-1beta ,CD8-Positive T-Lymphocytes ,Interleukin-23 ,Monocytes ,Interleukin 21 ,Cancer stem cell ,Cell Movement ,Stomach Neoplasms ,Cell Line, Tumor ,Immune Tolerance ,Cytotoxic T cell ,Humans ,Myeloid Progenitor Cells ,Interleukin 3 ,Aged ,Proportional Hazards Models ,CD40 ,Lymphokine-activated killer cell ,Hepatology ,biology ,Interleukin-6 ,Chemotaxis ,Macrophages ,Interleukin-17 ,Gastroenterology ,Dendritic Cells ,Middle Aged ,Flow Cytometry ,Prognosis ,Molecular biology ,Chemokine CXCL12 ,Coculture Techniques ,Phenotype ,Multivariate Analysis ,biology.protein ,Myeloid-derived Suppressor Cell ,Interleukin 12 ,Female ,Granulocytes - Abstract
Background & Aims CD8 + T cells that produce interleukin (IL)-17 (Tc17 cells) promote inflammation and have been identified in tumors. We investigated their role in the pathogenesis of gastric cancer. Methods We used flow cytometry analyses to determine levels and phenotype of Tc17 cells in blood and tumor samples from 103 patients with gastric cancer. We performed multivariate analysis to identify factors associated with overall survival using the Cox proportional hazards model. CD8 + T cells and monocytes were isolated and cocultured in an assay for induction of Tc17 cells. Tumor cells and myeloid-derived suppressor cells (MDSCs) were isolated and used in assays of Tc17 cell function. Results Tc17 cells with distinct cytokine and functional profiles were found in gastric tumor samples from patients. The percentage of Tc17 cells increased with tumor progression and was associated with overall survival time. Tumor-activated monocytes secreted IL-6, IL-1β, and IL-23, which promoted development of Tc17 cell populations. Supernatants from cultured Tc17 cells induced production of the chemokine CXCL12 by tumor cells; this promoted CXCR4-dependent migration of MDSCs and impaired functions of anti-tumor CD8 + cytotoxic T cells via a cell contact–dependent mechanism. Conclusions Percentages of Tc17 cells in gastric tumors are associated with survival times of patients. These cells promote chemotaxis of MDSCs, which might promote tumor progression.
- Published
- 2011