CD169+ macrophages identify and eliminate tumor cells in colorectal cancer through CD169/CD43 interaction and FasL-driven apoptosis

  • Cell Rep. 2025 Sep 26;44(10):116351. doi: 10.1016/j.celrep.2025.116351.
Junqing Hu  1 ,  Feilong Guo  2 ,  Congwei Han  3 ,  Qiqi Zhao  3 ,  Huaiqiang Yi  3 ,  Jinhao Xu  3 ,  Huijie Jia  3 ,  Yongjie Wu  3 ,  Lei Dong  3 ,  Xiaoming Kao  2 ,  Guoli Li  4 ,  Jiangning Chen  5 ,  Junfeng Zhang  6 ,  Zhen Huang  7
Affiliations
  • 1. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210023, China; NJU Xishan Institute of Applied Biotechnology, Xishan District, Wuxi, Jiangsu 214101, China.
  • 2. Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China.
  • 3. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210023, China.
  • 4. Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China. Electronic address: [email protected].
  • 5. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210023, China; State Key Laboratory of Analytical Chemistry for Life Sciences, Nanjing University, Nanjing, Jiangsu 210023, China. Electronic address: [email protected].
  • 6. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210023, China. Electronic address: [email protected].
  • 7. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210023, China; NJU Xishan Institute of Applied Biotechnology, Xishan District, Wuxi, Jiangsu 214101, China. Electronic address: [email protected].
PMID: 41016034 DOI: 10.1016/j.celrep.2025.116351
Abstract

Tumor-associated macrophages (TAMs) play key roles in tumor progression and therapy resistance. In colorectal Cancer (CRC), TAM heterogeneity challenges macrophage-targeted therapies, with certain antitumor macrophage subpopulations not yet fully characterized. This study bridges this gap by identifying a distinct subset of tumoricidal CD169+ macrophages. Increased infiltration of CD169+ macrophages was observed in CRC tissues, which was significantly associated with improved overall survival in patients with CRC. Deleting CD169+ macrophages in genetically engineered mouse models (MC38 orthotopic/ectopic and CD169DTR/+APCMin/+ intestinal adenoma) accelerated tumor growth. Integrated multi-omics data and functional assays, including cell coculture models and animal experiments with antibody blockade, reveal an antitumor mechanism in which CD169+ macrophages directly interact with CRC cells. This interaction, mediated by CD169/CD43 molecular engagements, leads to tumor cell Apoptosis via high levels of factor-related Apoptosis ligand (FasL). Our results not only deepen our understanding of the CRC tumor microenvironment but also open avenues for Cancer Immunotherapy targeting.

Keywords
CD169(+) macrophages; CD43; CP: Cancer; CP: Immunology; FasL; colorectal cancer.
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