Cellular & Molecular Immunology, 12 June, 2023, DOI：https://doi.org/10.1038/s41423-023-01047-4

Hierarchical fluctuation shapes a dynamic flow linked to states of consciousness

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

Abstract

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.

Article link：https://www.nature.com/articles/s41423-023-01047-4