Journal Article

Activated cytotoxic lymphocytes promote tumor progression by increasing the ability of 3LL tumor cells to mediate MDSC chemoattraction via Fas signaling

Fei Yang Yinxiang Wei Zhijian Cai Lei Yu Lingling Jiang Chengyan Zhang Huanmiao Yan Qingqing Wang Xuetao Cao Tingbo Liang Jianli Wang

2015

Overview

The Fas/FasL system transmits intracellular apoptotic signaling, inducing cell apoptosis. However, Fas signaling also exerts non-apoptotic functions in addition to inducing tumor cell apoptosis. For example, Fas signaling induces lung cancer tumor cells to produce prostaglandin E2 （PGE2） and recruit myeloid-derived suppressor cells （MDSCs）. Activated cytotoxic T lymphocytes （CTLs） induce and express high levels of FasL, but the effects of Fas activation initiated by FasL in CTLs on apoptosis-resistant tumor cells remain largely unclear. We purified activated CD8^＋ T cells from OT-1 mice, evaluated the regulatory effects of Fas activation on tumor cell escape and investigated the relevant mechanisms. We found that CTLs induced tumor cells to secrete PGE2 and increase tumor cell-mediated chemoattraction of MDSCs via Fas signaling, which was favorable to tumor growth. Our results indicate that CTLs may participate in the tumor immune evasion process. To the best of our knowledge, this is a novel mechanism by which CTLs play a role in tumor escape. Our findings implicate a strategy to enhance the antitumor immune response via reduction of negative immune responses to tumors promoted by CTLs through Fas signaling.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Animals / Antibodies / Antitumor activity / Apoptosis / Apoptosis - genetics / Biomedical and Life Sciences / Biomedicine / Carcinogenesis / CD8 antigen / Cell activation / Cell Line, Tumor / Chemotaxis - genetics / Cytotoxicity / Dinoprostone - metabolism / Fas Ligand Protein - genetics / Fas Ligand Protein - metabolism / fas Receptor - genetics / fas Receptor - metabolism / FasL / FasL protein / Female / Immunology / Immunosuppression / Intracellular signalling / Lung cancer / Lung Neoplasms - immunology / Lymphocyte Activation / Lymphocytes T / MDSC / Medical Microbiology / Mice / Mice, Inbred C57BL / Mice, Transgenic / Microbiology / Myeloid Cells - physiology / Prostaglandin E2 / research-article / RNA, Small Interfering - genetics / Signal Transduction - genetics / Suppressor cells / T-Lymphocytes, Cytotoxic - physiology / Tumor cells / Tumor Escape / Vaccine / 介导 / 凋亡信号 / 激活 / 细胞毒性T淋巴细胞 / 肿瘤细胞凋亡 / 趋化