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Vol. 64 No. 12: Issue 12

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SMAR1 promotes immune escape of Tri-negative Breast Cancer through a mechanism involving T-bet/PD-1 Axis

https://doi.org/10.14715/cmb/2018.64.12.14
Wang Xiaohua
Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China
Xu Hongxia
Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China
Deng Rong
Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China
Wu Pingping
Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China
Huang Xing
Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China
Zhu Yichao
Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China
Chen Cheng
Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China

Corresponding Author(s) : Wang Xiaohua

zg1274@163.com

Cellular and Molecular Biology, Vol. 64 No. 12: Issue 12

Abstract

This study was aimed at investigating the specific molecular mechanisms involved in the regulation of immune escape of triple-negative breast cancer (TNBC) by SMRI, so as to provide a new clinical treatment target for the disease. Mouse original 4T1 breast cancer cells were inoculated subcutaneously in BALB/C to establish TNBC mouse model. CD8+T cells with immunological effects were selected from mouse thymus glands for primary culture. The CD8+positive T cells were infected with lentivirus interference vectors, and the proliferation of CD8+ T cells were determined by trypan blue staining and flow cytometry. CD8+T cells and 4T1 cells were cultured together so as to determine the cytotoxic effects of SMAR1-downregulated CD8+ T cells on tumor cells and the expression of cytokines (IFN-γ, TNF-α, IL-2, IL-4 and IL-6). The expressions of SMAR1, T-bet and PD-1 were assayed by Western blot. SMAR1-downregulated CD8+T cells were injected into 4T1 tumor-bearing mice through the caudal vein, and the growth of tumor in mice was monitored. Following the infection of CD8+T cells with SMAR1-downregulated lentiviral system, cell apoptosis level was decreased significantly (control vs. sh-SMAR1: 32.23 ± 12.4 % vs. 18.28 ± 8.93 %, p < 0.05). Results from trypan blue staining experiments showed that the proliferation of CD8+ T cells in the SMAR1-downregulated group was significantly increased; SMAR1-downregulated CD8+ T cells promoted the production of IFN-γ, TNF-α, IL-2, IL-4 and IL-6 in 4T1 breast cancer cells (p < 0.05). Western blot showed that SMAR1 down-regulation led to significant upregulation of T-bet, while PD-1 was downregulated, when compared to the control group (p < 0.05). The downregulation of SMAR1 was associated with significant reduction in tumor size in mice (p < 0.05). SMAR1 downregulation enhances the tumor killing effect of CD8+T cells by activating T-bet and down-regulating PD-1

Keywords

SMAR1 T-bet PD-1 Triple negative breast cancer Immune escape.
Xiaohua, W., Hongxia, X., Rong, D., Pingping, W., Xing, H., Yichao, Z., & Cheng, C. (2018). SMAR1 promotes immune escape of Tri-negative Breast Cancer through a mechanism involving T-bet/PD-1 Axis. Cellular and Molecular Biology, 64(12), 70–75. https://doi.org/10.14715/cmb/2018.64.12.14
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