2. Academic Validation
  3. A subpopulation of CD146+ macrophages enhances antitumor immunity by activating the NLRP3 inflammasome

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

  • Cell Mol Immunol. 2023 Jun 12. doi: 10.1038/s41423-023-01047-4.
Lin Jing # 1,  Yunhe An # 2,  Tanxi Cai # 3 4,  Jianquan Xiang 1 5,  Baoming Li 2,  Jiang Guo 6,  Xinran Ma 1 5,  Ling Wei 2,  Yanjie Tian 2,  Xiaoyan Cheng 2,  Xuehui Chen 1,  Zheng Liu 1,  Jing Feng 1,  Fuquan Yang 7 8 9,  Xiyun Yan 10 11 12,  Hongxia Duan 13
Affiliations

Affiliations

  • 1 Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • 2 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.
  • 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 Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. fqyang@ibp.ac.cn.
  • 8 Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. fqyang@ibp.ac.cn.
  • 9 College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China. fqyang@ibp.ac.cn.
  • 10 Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. yanxy@ibp.ac.cn.
  • 11 College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China. yanxy@ibp.ac.cn.
  • 12 Joint Laboratory of Nanozymes in Zhengzhou University, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China. yanxy@ibp.ac.cn.
  • 13 Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. cherryshoen@ibp.ac.cn.
  • # Contributed equally.
PMID: 37308559 DOI: 10.1038/s41423-023-01047-4
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.

Keywords

CD146; Inflammasome; TMEM176B; Tumor immunotherapy; Tumor-associated macrophages.

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