PMID- 32278689 OWN - NLM STAT- MEDLINE DCOM- 20201231 LR - 20201231 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 392 IP - 2 DP - 2020 Jul 15 TI - Twist1 promotes dendritic cell-mediated antitumor immunity. PG - 112003 LID - S0014-4827(20)30225-1 [pii] LID - 10.1016/j.yexcr.2020.112003 [doi] AB - 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-gamma, 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. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Luo, Yuechen AU - Luo Y AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Institute of Hematology & Hospital of Blood Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. FAU - Chen, Jiadi AU - Chen J AD - Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China. FAU - Liu, Maolan AU - Liu M AD - Department of Hematology, The First Affiliated Hospital of Kunming Medical University, Hematology Research Center of Yunnan Province, Kunming, 650032, China. FAU - Chen, Song AU - Chen S AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Institute of Hematology & Hospital of Blood Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. FAU - Su, Xiuhua AU - Su X AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Institute of Hematology & Hospital of Blood Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. FAU - Su, Jing AU - Su J AD - Department of Hematology, The First Affiliated Hospital of Kunming Medical University, Hematology Research Center of Yunnan Province, Kunming, 650032, China. FAU - Zhao, Chunxiao AU - Zhao C AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Institute of Hematology & Hospital of Blood Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. FAU - Han, Zhongchao AU - Han Z AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Institute of Hematology & Hospital of Blood Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. FAU - Shi, Mingxia AU - Shi M AD - Department of Hematology, The First Affiliated Hospital of Kunming Medical University, Hematology Research Center of Yunnan Province, Kunming, 650032, China. Electronic address: shmxia2002@sina.com. FAU - Ma, Xiaotong AU - Ma X AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Institute of Hematology & Hospital of Blood Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. Electronic address: maxt@ihcams.ac.cn. FAU - Huang, Huifang AU - Huang H AD - Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, China. Electronic address: huanghuif@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200410 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Antigens, Neoplasm) RN - 0 (Twist-Related Protein 1) RN - 136253-27-5 (Twist1 protein, mouse) SB - IM MH - Animals MH - Antigens, Neoplasm/immunology MH - CD4-Positive T-Lymphocytes/*immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - Dendritic Cells/*immunology/metabolism/pathology MH - Immunity, Cellular/*immunology MH - Lymphocytes, Tumor-Infiltrating/*immunology MH - Melanoma, Experimental/*immunology/metabolism/pathology MH - Mice MH - Mice, Knockout MH - Twist-Related Protein 1/*physiology OTO - NOTNLM OT - Antitumor OT - Dendritic cells OT - IFN-gamma OT - Twist1 COIS- Declaration of competing interest All authors have declared no conflicts of interest. EDAT- 2020/04/13 06:00 MHDA- 2021/01/01 06:00 CRDT- 2020/04/13 06:00 PHST- 2019/11/25 00:00 [received] PHST- 2020/04/03 00:00 [revised] PHST- 2020/04/05 00:00 [accepted] PHST- 2020/04/13 06:00 [pubmed] PHST- 2021/01/01 06:00 [medline] PHST- 2020/04/13 06:00 [entrez] AID - S0014-4827(20)30225-1 [pii] AID - 10.1016/j.yexcr.2020.112003 [doi] PST - ppublish SO - Exp Cell Res. 2020 Jul 15;392(2):112003. doi: 10.1016/j.yexcr.2020.112003. Epub 2020 Apr 10.