A subpopulation of CD146^(+) macrophages enhances antitumor immunity by activating the NLRP3 inflammasome  

作　　者：Lin Jing Yunhe An Tanxi Cai Jianquan Xiang Baoming Li Jiang Guo Xinran Ma Ling Wei Yanjie Tian Xiaoyan Cheng Xuehui Chen Zheng Liu Jing Feng Fuquan Yang Xiyun Yan Hongxia Duan 

机构地区：[1]Key Laboratory of Protein and Peptide Pharmaceutical,Institute of Biophysics,Chinese Academy of Sciences,Bejing 100101,China [2]Institute of Analysis and Testing,Beijing Academy of Science and Technology(Bejing Center for Physical and Chemical Analysis),No.7 Fengxian Middle Street,Haidian District,Beijing 100094,China [3]Sino-Danish College,University of Chinese Academy of Sciences,Beijing,100049,China [4]Laboratory of Proteomics,Institute of Biophysics,Chinese Academy of Sciences,Beijing,China [5]College of Life Sciences,University of Chinese Academy of Sciences,Beijing,100049,China [6]Department of Interventional Oncology,Beijing Ditan Hospital,Capital Medical University,No.8 Jingshun East Street,Chaoyang District,Beijing,100015,China [7]Joint Laboratory of Nanozymes in Zhengzhou University,School of Basic Medical Sciences,Zhengzhou University,Zhengzhou,450001,China

出　　处：《Cellular & Molecular Immunology》2023年第8期908-923,共16页中国免疫学杂志（英文版）

基　　金：supported in part by grants from the Beijing Natural Science Foundation of China(Grant No.7192123,7222117);the National Natural Science Foundation of China(Grant No.31770793,82000812);the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.2018122).

摘　　要：As one of the main tumor-infiltrating immune cell types, tumor-associated macrophages (TAMs) determine the efficacy of immunotherapy. However, limited knowledge about their phenotypically and functionally heterogeneous nature restricts their application in tumor immunotherapy. In this study, we identified a subpopulation of CD146+ TAMs that exerted antitumor activity in both human samples and animal models. CD146 expression in TAMs was negatively controlled by STAT3 signaling. Reducing this population of TAMs promoted tumor development by facilitating myeloid-derived suppressor cell recruitment via activation of JNK signaling. Interestingly, CD146 was involved in the NLRP3 inflammasome-mediated activation of macrophages in the tumor microenvironment, partially by inhibiting transmembrane protein 176B (TMEM176B), an immunoregulatory cation channel. Treatment with a TMEM176B inhibitor enhanced the antitumor activity of CD146+ TAMs. These data reveal a crucial antitumor role of CD146+ TAMs and highlight the promising immunotherapeutic approach of inhibiting CD146 and TMEM176B.

关 键 词：Tumor-associated macrophages CD146 INFLAMMASOME TMEM176B Tumor immunotherapy 

分 类 号：R730.51[医药卫生—肿瘤]