Activated cytotoxic lymphocytes promote tumor progression by increasing the ability of 3LL tumor cells to mediate MDSC chemoattraction via Fas signaling.
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.
1] Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China [2] The Second Affiliated Hospital, Hangzhou, Zhejiang, China.
Fei
F
Yang
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Yinxiang
Y
Wei
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Zhijian
Z
Cai
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Lei
L
Yu
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Lingling
L
Jiang
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Chengyan
C
Zhang
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Huanmiao
H
Yan
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Qingqing
Q
Wang
1] Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China [2] Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, China.
Xuetao
X
Cao
The Second Affiliated Hospital, Hangzhou, Zhejiang, China.
Tingbo
T
Liang
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Jianli
J
Wang
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002633:Chemotaxis / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D007165:Immunosuppression Therapy; D008175:Lung Neoplasms / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D019139:Tumor Escape; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D053222:Fas Ligand Protein; D034741:RNA, Small Interfering; D019014:fas Receptor; D015232:Dinoprostone