CXCR2+ MDSCs promote breast cancer progression by inducing EMT and activated T cell exhaustion
Metrics: PDF 2968 views | HTML 4020 views | ?
Ha Zhu1, Yan Gu1, Yiquan Xue1, Ming Yuan1, Xuetao Cao1 and Qiuyan Liu1
1National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China
Qiuyan Liu, email: [email protected]
Keywords: CXCR2+ MDSCs; breast cancer; tumor metastasis; EMT; T cells exhaustion
Received: June 13, 2017 Accepted: November 14, 2017 Published: December 07, 2017
Although myeloid-derived suppressor cells (MDSCs) have been demonstrated to contribute to tumor initiation, progression and metastasis, however, which MDSC subsets are preferentially expanded and activated, and what’s the key molecular mechanism responsible for specific MDSC subsets in promoting tumor progression need to be fully addressed. Here we identify that Ly6GmiLy6CloCD11b+CXCR2+ subpopulation (named CXCR2+ MDSCs) are predominately expanded and recruited in systemic and local tumor microenvironment during breast cancer progression and metastasis. The proportion of CXCR2+ MDSCs is inversely correlated with the infiltration of CD4+ or CD8+ T cells. Besides, CXCR2+ MDSCs promote breast cancer growth and metastasis to lung and/or lymph node in vivo. Furthermore, CXCR2+ MDSCs induce epithelial mesenchymal transition (EMT) of breast cancer cells via IL-6. Moreover, CXCR2+ MDSCs upregulate the expression of immunosuppressive molecules programmed cell death protein 1(PD1), PD1 ligand 1 (PDL1), lymphocyte activation gene 3 protein (LAG3), cytotoxic T lymphocyte antigen 4 (CTLA4), and T cell immunoglobulin domain and mucin domain protein 3 (TIM3) on CD4+ or CD8+ T cells, and induce exhaustion of the activated T cells partially via IFN-γ. These results demonstrate that CXCR2+ MDSCs accelerate breast cancer progression via directly inducing cancer cell EMT and indirectly promoting T cell exhaustion, suggesting that CXCR2+ MDSCs may be a potential therapeutic target of breast cancer.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.