Cancer immunotherapy has revolutionized cancer treatment by leveraging the immune system to attack tumors. However, its effectiveness is often hindered by the immunosuppressive tumor microenvironment (TME), where a complex interplay of tumor, stromal, and immune cells undermines antitumor responses and allows tumors to evade immune detection. This review explores innovative strategies to modify the TME and enhance immunotherapy outcomes, focusing on the therapeutic potential of engineered bacteria. These bacteria exploit the unique characteristics of the TME, such as abnormal vasculature and immune suppression, to selectively accumulate in tumors. Genetically modified bacteria can deliver therapeutic agents, including immune checkpoint inhibitors and cytokines, directly to tumor sites. This review highlights how bacterial therapeutics can target critical immune cells within the TME, such as myeloid-derived suppressor cells and tumor-associated macrophages, thereby promoting antitumor immunity. The combination of bacterial therapies with immune checkpoint inhibitors or adoptive cell transfer presents a promising strategy to counteract immune suppression. Continued research in this area could position bacterial agents as a powerful new modality to reshape the TME and enhance the efficacy of cancer immunotherapy, particularly for tumors resistant to conventional treatments.
癌症免疫疗法通过调动免疫系统攻击肿瘤，已彻底改变了癌症治疗格局。然而，其疗效常受限于免疫抑制性肿瘤微环境（TME）——肿瘤细胞、基质细胞与免疫细胞在此形成复杂相互作用，削弱抗肿瘤免疫应答并帮助肿瘤逃避免疫监视。本综述探讨了改造肿瘤微环境以提升免疫治疗效果的创新策略，重点关注工程化细菌的治疗潜力。这类细菌能利用肿瘤微环境异常血管结构和免疫抑制等特征，实现肿瘤部位选择性定植。经基因改造的细菌可直接向肿瘤部位递送免疫检查点抑制剂、细胞因子等治疗剂。本文系统阐述了细菌疗法如何靶向肿瘤微环境中髓源性抑制细胞、肿瘤相关巨噬细胞等关键免疫细胞，从而激活抗肿瘤免疫。细菌疗法与免疫检查点抑制剂或过继性细胞疗法的联合应用，为逆转免疫抑制提供了前景广阔的新策略。该领域的持续研究有望使细菌制剂发展成为重塑肿瘤微环境、增强癌症免疫疗效的新型强效手段，尤其为常规治疗耐受的肿瘤类型带来新的治疗希望。
Harnessing Bacterial Agents to Modulate the Tumor Microenvironment and Enhance Cancer Immunotherapy
肿瘤(癌症)患者之家