Thomas Christina James, Delgado Kaylee, Sawant Kamlesh, Roy Jacob, Gupta Udit, Song Carly Shaw, Poojary Rayansh, de Figueiredo Paul, Song Jianxun
Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, MREB II, Room 3344, 8447 John Sharp Parkway, Bryan, TX 77807, USA.
Department of Molecular Microbiology and Immunology, The University of Missouri School of Medicine, Columbia, MO 65212, USA.
Cancers (Basel). 2024 Nov 13;16(22):3810. doi: 10.3390/cancers16223810.
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.
癌症免疫疗法通过利用免疫系统攻击肿瘤，彻底改变了癌症治疗方式。然而，其有效性常常受到免疫抑制性肿瘤微环境（TME）的阻碍，在该微环境中，肿瘤、基质和免疫细胞之间复杂的相互作用破坏了抗肿瘤反应，并使肿瘤能够逃避免疫检测。本综述探讨了改变肿瘤微环境和提高免疫治疗效果的创新策略，重点关注工程菌的治疗潜力。这些细菌利用肿瘤微环境的独特特征，如异常血管生成和免疫抑制，选择性地在肿瘤中积聚。基因工程改造的细菌可以将治疗剂，包括免疫检查点抑制剂和细胞因子，直接递送至肿瘤部位。本综述强调了细菌疗法如何靶向肿瘤微环境中的关键免疫细胞，如髓源性抑制细胞和肿瘤相关巨噬细胞，从而促进抗肿瘤免疫。细菌疗法与免疫检查点抑制剂或过继性细胞转移相结合，是一种对抗免疫抑制的有前景的策略。该领域的持续研究可能会使细菌制剂成为重塑肿瘤微环境和提高癌症免疫治疗疗效的强大新方法，特别是对于对传统治疗耐药的肿瘤。
