Open AccessTGF-β1 promotes colorectal cancer immune escape by elevating B7-H3 and B7-H4viathe miR-155/miR-143 axis
Author(s) -
Xinru Zhou,
Yong Mao,
Jianjie Zhu,
Meng Fang,
Qi Chen,
Lihua Tao,
Rui Li,
Fengqing Fu,
Cuiping Liu,
Hu Y,
Weipeng Wang,
Hongjian Zhang,
Dong Hua,
Weichang Chen,
Xueguang Zhang
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.11950
Subject(s) - transforming growth factor , cancer research , immune system , downregulation and upregulation , biology , colorectal cancer , transforming growth factor beta , cancer cell , microrna , secretion , microbiology and biotechnology , cancer , immunology , medicine , gene , endocrinology , biochemistry
Transforming growth factor-beta 1 (TGF-β1) suppresses T cell function, promoting tumor immune escape. Yet, whether the depression of TGF-β1 on T cell function is mediated by co-inhibitory molecules B7-H3 and B7-H4 remains largely unclear. Here, we demonstrated that TGF-β1 elevated the expression of miR-155 in colorectal cancer cells through SMAD3 and SMAD4. The upregulated miR-155 attenuated miR-143 by inhibiting its direct target, the transcription factor CEBPB. Consequently, the direct target genes of miR-143, B7-H3 and B7-H4, were augmented in the cytoplasm and membrane of tumor cells. Over-expression of B7-H3 and B7-H4 in HCT-116 cells induced T cells to secrete TGF-β1 and the immunosuppressive cytokines IL-2, IL-6, and IL-17. Restoration of miR-143 inhibited the growth of HCT-116 xenograft tumors in mice, and also repressed the expression of B7-H3 and B7-H4 in the tumors. Thus, this study reveals the mechanism by which TGF-β1 leads to T cell-mediated tumor evasion through an increase in B7-H3 and B7-H4 expression.