Manole Simin, Nguyen Dinh-Huy, Min Jung-Joon, Zhou Shibin, Forbes Neil
Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA, USA.
Institute for Molecular Imaging and Theranostics, Chonnam National University, Hwasun, Jeonnam 58128, South Korea.
Med. 2025 Jan 10;6(1):100549. doi: 10.1016/j.medj.2024.11.002. Epub 2024 Dec 16.
Immunotherapy with checkpoint blockade has shown remarkable efficacy in many patients with a variety of different types of cancer. However, the majority of patients with cancer have yet to benefit from this revolutionary therapy. Studies have shown that checkpoint blockade works best against immune-inflamed tumors characterized by the presence of tumor-infiltrating lymphocytes (TILs). In this review, we summarize studies using live tumor-targeting bacteria to treat cancer and describe various strategies to engineer the tumor-targeting bacteria for maximized immunoregulatory effects. We propose that tumor-localized infections by such engineered bacteria can create an immune microenvironment in favor of a more effective antitumor immunity with or without other therapies, such as immune checkpoint blockade (ICB). Finally, we will briefly outline some exemplary oncology clinical trials involving ICB plus live therapeutic bacteria, with a focus on their ability to modulate antitumor immune responses.
免疫检查点阻断免疫疗法已在许多患有各种不同类型癌症的患者中显示出显著疗效。然而，大多数癌症患者尚未从这种革命性疗法中受益。研究表明，检查点阻断对以肿瘤浸润淋巴细胞（TILs）存在为特征的免疫炎症性肿瘤效果最佳。在本综述中，我们总结了使用靶向活肿瘤细菌治疗癌症的研究，并描述了改造靶向肿瘤细菌以实现最大免疫调节作用的各种策略。我们提出，此类工程菌引起的肿瘤局部感染可在有或没有其他疗法（如免疫检查点阻断（ICB））的情况下，创造有利于更有效抗肿瘤免疫的免疫微环境。最后，我们将简要概述一些涉及ICB加活治疗性细菌的肿瘤学临床试验范例，重点关注它们调节抗肿瘤免疫反应的能力。
