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

Cellular & Molecular Immunology volume 12, pages 66–76 (2015)Cite this article

Abstract

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.

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Acknowledgements

The work was supported by the Specialized Research Fund for the Chinese National 973 Project (2013CB530502), the Doctoral Program of Higher Education of China (20110101110105), the Project of the Chinese National Nature Science Foundation (31370902, 31070795, 31270944), the Projects in Science and Technology Plan of Zhejiang Province (013C33G2010434) of China, the National Key Science and Technology Specific Project of China (2012ZX10002006), the National High Technology Research and Development Program (2012AA020900), and the Project of the Chinese National Natural Science Fund Committee for Talent Cultivation (J1103603).

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Author notes

  1. Fei Yang, Yinxiang Wei and Zhijian Cai: These authors contributed equally to this work.

  2. Dr TB Liang, The Second Affiliated Hospital, Hangzhou 310009, Zhejiang, China. E-mail: liangtingbo@zju.edu.cn

  3. Dr JL Wang, Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China. E-mail: jlwang@zju.edu.cn

Authors and Affiliations

  1. Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China

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

  2. The Second Affiliated Hospital, Hangzhou, Zhejiang, China

    Fei Yang & Tingbo Liang

  3. Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, China

    Xuetao Cao

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Yang, F., Wei, Y., Cai, Z. et al. Activated cytotoxic lymphocytes promote tumor progression by increasing the ability of 3LL tumor cells to mediate MDSC chemoattraction via Fas signaling. Cell Mol Immunol 12, 66–76 (2015). https://doi.org/10.1038/cmi.2014.21

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