Harnessing engineered bacteria for revolutionizing cancer immunotherapy

Cancer immunotherapy has markedly improved patient survival and quality of life, yet its benefits remain limited by heterogeneous efficacy and immune-related toxicities. Increasing evidence highlights the complex roles of bacteria in tumor initiation, progression, and therapeutic response. Leveraging their inherent tumor-targeting and immune-modulating properties, bacteria can be reprogrammed through genetic engineering, synthetic biology, and biomaterial integration into safe, controllable, and multifunctional agents. Engineered bacteria and their derivatives, such as outer membrane vesicles, have shown promise in mediating direct anti-tumor effects, enhancing immunotherapy, and serving as platforms for drug delivery and cancer vaccines. This review summarizes current advances in genetically engineered bacteria, bacteria-nanomaterials biohybrid systems, engineered bacterial derivatives, and community-engineered bacteria, focusing on their mechanisms, therapeutic applications, and clinical translation. Finally, we discuss the current challenges and future opportunities in advancing engineered bacteria as safe and effective tools in the immunotherapy era.