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

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外文摘要：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.

外文关键词：

Tumor-associated macrophagesCD146InflammasomeTMEM176BTumor immunotherapy

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

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作者单位：

Key Laboratory of Protein and Peptide Pharmaceutical,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China

Institute of Analysis and Testing,Beijing Academy of Science and Technology(Beijing Center for Physical and Chemical Analysis),No.7 Fengxian Middle Street,Haidian District,Beijing 100094,China

Sino-Danish College,University of Chinese Academy of Sciences,Beijing 100049,China

Laboratory of Proteomics,Institute of Biophysics,Chinese Academy of Sciences,Beijing,China

College of Life Sciences,University of Chinese Academy of Sciences,Beijing 100049,China

Department of Interventional Oncology,Beijing Ditan Hospital,Capital Medical University,No.8 Jingshun East Street,Chaoyang District,Beijing 100015,China

Joint Laboratory of Nanozymes in Zhengzhou University,School of Basic Medical Sciences,Zhengzhou University,Zhengzhou,450001,China

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基金：

Beijing Natural Science Foundation of ChinaBeijing Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaYouth Innovation Promotion Association of Chinese Academy of Sciences

项目编号：

7192123722211731770793820008122018122

出版年：

2023

DOI：

10.1038/s41423-023-01047-4

中国免疫学杂志(英文版)

中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI

影响因子：0.731

ISSN：1672-7681

年,卷(期)：2023.20(8)

参考文献量42