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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2025, Vol. 30 ›› Issue (3): 297-312.doi: 10.12092/j.issn.1009-2501.2025.03.002

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Engineered bacteria modulate tumor-associated macrophages to enhance immunotherapy

WANG Long, WANG Yuchen, GUO Yilin, WU Jinhui   

  1. Medical School of Nanjing University, Nanjing 210093, Jiangsu, China
  • Received:2024-07-29 Revised:2024-09-03 Online:2025-03-26 Published:2025-02-28

Abstract:

The immunosuppressive tumor microenvironment significantly limits the efficacy of immunotherapy. Tumor-associated macrophages (TAMs), the most abundant immune cells in the tumor microenvironment, often exhibit an immunosuppressive M2 phenotype, contributing to this immunosuppressive landscape. Modulating TAMs to adopt anti-tumor phenotypes can enhance immunotherapy outcomes and inhibit tumor progression.In recent years, tumor immunotherapy leveraging engineered bacteria has garnered considerable attention. Bacteria possess the ability to target tumors, preferentially colonizing tumor regions, and contain abundant pathogen-associated molecular patterns that effectively activate TAMs within the immunosuppressive tumor environment. This activation enhances the tumoricidal and clearance capabilities of TAMs. With the rapid advancements in synthetic biology, engineered bacteria have emerged as a potent therapeutic modality for immunotherapy, leading to increased focus on the regulation of TAMs by engineered bacteria.This paper first outlines clinical studies on targeted TAMs therapy and engineered bacteria-based tumor therapy. It then reviews recent advancements in bacterial regulation of TAMs, detailing how engineered bacteria enhance TAM recruitment, improve TAM phagocytosis, and remodel TAM phenotypes. Modulating TAMs with engineered bacteria presents a promising therapeutic strategy and introduces a novel approach in tumor immunotherapy.

Key words: engineered bacteria, tumor-associated macrophages, immunotherapy, tumor microenvironment

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