Twist1 promotes dendritic cell-mediated antitumor immunity.

Yuechen Luo, Jiadi Chen, Maolan Liu, Song Chen, Xiuhua Su, Jing Su, Chunxiao Zhao, Zhongchao Han, Mingxia Shi, Xiaotong Ma, Huifang Huang

Experimental cell research 2020 Jul 15

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Dendritic cells (DCs) play a central role in autoimmunity, immune homeostasis, and presentation of tumor antigens to T cells in order to prime antitumor responses. The number of tumor-infiltrating DCs is associated with survival and prognosis in cancer. Twist1 is a well-known regulator of tumor initiation and promotion, but whether and how DC-derived Twist1 regulates antitumor responses remains poorly understood. Here, we generated a mouse line with Twist1 conditionally depleted in DCs and found that Twist1-deficiency in DCs did not affect the DCs and T cell homeostasis under steady-state conditions; however, in melanoma models, the proportion of conventional DCs (cDCs) in draining lymph nodes (DLNs) was significantly decreased. Accordingly, a decreased ratio and number of tumor-infiltrating cDCs were observed, which reduced the recruitment of tumor-infiltrating T cells. Furthermore, production of IFN-γ, a crucial antitumor factor, by T cells, was dramatically decreased, which can further dampen the T cell antitumor functions. Collectively, our data indicate that Twist1 in DCs regulates antitumor functions by maintain the number of tumor-infiltrating DCs and T cells, and their antitumor activity. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Yuechen Luo, Jiadi Chen, Maolan Liu, Song Chen, Xiuhua Su, Jing Su, Chunxiao Zhao, Zhongchao Han, Mingxia Shi, Xiaotong Ma, Huifang Huang. Twist1 promotes dendritic cell-mediated antitumor immunity. Experimental cell research. 2020 Jul 15;392(2):112003