传统疗法失败的主要原因是肿瘤微环境（TME）的异质性和复杂性。许多恶性肿瘤会重新编程其表面抗原以逃避免疫监视，导致抗原呈递细胞减少并阻碍 T 细胞激活。近年来，细菌介导的癌症免疫疗法得到了广泛的研究。科学家利用合成生物学和纳米技术巧妙地改造了细菌，以增强其生物安全性和高肿瘤特异性，从而产生强大的抗癌免疫反应。为了增强抗肿瘤功效，利用工程细菌有效地输送治疗蛋白、细胞因子、纳米颗粒和化疗药物。这篇综述提供了对溶瘤细菌疗法的全面了解，涵盖细菌设计和 TME 内复杂的相互作用。此外，它还对当前用于细菌内部和外部修饰的技术进行了深入比较，以最大限度地提高其治疗效果。最后，我们概述了溶瘤细菌疗法临床应用中面临的挑战和机遇。版权所有 © 2024。由 Elsevier Inc. 出版。

The major reason for the failure of conventional therapies is the heterogeneity and complexity of tumor microenvironments (TMEs). Many malignant tumors reprogram their surface antigens to evade the immune surveillance, leading to reduced antigen-presenting cells and hindered T-cell activation. Bacteria-mediated cancer immunotherapy has been extensively investigated in recent years. Scientists have ingeniously modified bacteria using synthetic biology and nanotechnology to enhance their biosafety with high tumor specificity, resulting in robust anticancer immune responses. To enhance the antitumor efficacy, therapeutic proteins, cytokines, nanoparticles, and chemotherapeutic drugs have been efficiently delivered using engineered bacteria. This review provides a comprehensive understanding of oncolytic bacterial therapies, covering bacterial design and the intricate interactions within TMEs. Additionally, it offers an in-depth comparison of the current techniques used for bacterial modification, both internally and externally, to maximize their therapeutic effectiveness. Finally, we outlined the challenges and opportunities ahead in the clinical application of oncolytic bacterial therapies.Copyright © 2024. Published by Elsevier Inc.