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中国临床药理学与治疗学 ›› 2025, Vol. 30 ›› Issue (3): 297-312.doi: 10.12092/j.issn.1009-2501.2025.03.002

• 纳米药理与治疗新技术专栏 • 上一篇    下一篇

工程菌调控肿瘤相关巨噬细胞增强免疫治疗

王龙,王宇辰,郭奕霖,吴锦慧   

  1. 南京大学医学院,南京  210093,江苏
  • 收稿日期:2024-07-29 修回日期:2024-09-03 出版日期:2025-03-26 发布日期:2025-02-28
  • 通讯作者: 吴锦慧,男,博士,教授,博士生导师,研究方向:智能药物递送系统。 E-mail: wuj@nju.edu.cn
  • 作者简介:王龙,男,硕士,研究方向:微生物载体与免疫。 E-mail: wanglongwl@smail.nju.edu.cn
  • 基金资助:
    国家自然科学基金面上项目(32171372)

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

摘要:

肿瘤免疫抑制微环境限制了免疫治疗的疗效。肿瘤相关巨噬细胞(TAMs)是肿瘤微环境中含量最丰富的免疫细胞,表现出免疫抑制性的M2型并促进肿瘤免疫抑制微环境的形成。调控TAMs为抗肿瘤表型能够增强免疫治疗并抑制肿瘤生长。近年来,基于工程菌的肿瘤免疫治疗手段备受关注。细菌不仅能够靶向肿瘤并优先定植于肿瘤区域,而且含有丰富的病原体相关分子模式(DAMPs),能够在肿瘤免疫抑制环境中有效激活TAMs,增强TAMs对肿瘤的杀伤和清除。随着合成生物学的迅速发展,工程菌成为一种有效的免疫治疗模式,越来越多的研究关注到工程菌调控TAMs的作用。本文首先介绍了靶向TAMs治疗和工程菌肿瘤治疗的临床研究,随后梳理了细菌调控TAMs的最新进展,从增强TAMs招募、提高TAMs吞噬能力和重塑TAMs表型三个方面详细概括总结了工程菌对TAMs的调控作用。工程菌调控TAMs提供了一种有前途的治疗策略,是肿瘤免疫治疗的新方向。

关键词: 工程菌, 肿瘤相关巨噬细胞, 免疫治疗, 肿瘤微环境

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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