Immunotherapy has revolutionized the treatment of cancer but continues to be constrained by limited response rates, acquired resistance, toxicities and high costs, which necessitates the development of new, innovative strategies. The discovery of a connection between the human microbiota and cancer dates back 4,000 years, when local infection was observed to result in tumour eradication in some individuals. However, the true oncological relevance of the intratumoural microbiota was not recognized until the turn of the twentieth century. The intratumoural microbiota can have pivotal roles in both the pathogenesis and treatment of cancer. In particular, intratumoural bacteria can either promote or inhibit cancer growth via remodelling of the tumour microenvironment. Over the past two decades, remarkable progress has been made preclinically in engineering bacteria as agents for cancer immunotherapy; some of these bacterial products have successfully reached the clinical stages of development. In this Review, we discuss the characteristics of intratumoural bacteria and their intricate interactions with the tumour microenvironment. We also describe the many strategies used to engineer bacteria for use in the treatment of cancer, summarizing contemporary data from completed and ongoing clinical trials. The work described herein highlights the potential of bacteria to transform the landscape of cancer therapy, bridging ancient wisdom with modern scientific innovation.

免疫疗法已经彻底改变了癌症的治疗，但仍然受到有限的反应率、获得性耐药性、毒性和高成本的限制，这需要开发新的创新策略。人类微生物群与癌症之间联系的发现可以追溯到 4,000 年前，当时观察到局部感染导致一些个体的肿瘤被根除。然而，直到 20 世纪之交，肿瘤内微生物群的真正肿瘤学相关性才得到认识。肿瘤内微生物群在癌症的发病机制和治疗中都起着关键作用。特别是，肿瘤内细菌可以通过重塑肿瘤微环境来促进或抑制癌症生长。在过去的二十年里，在将细菌工程化为癌症免疫疗法的药物方面取得了显著的临床前进展;其中一些细菌产品已成功进入临床开发阶段。在这篇综述中，我们讨论了肿瘤内细菌的特征及其与肿瘤微环境的复杂相互作用。我们还描述了用于改造细菌以用于治疗癌症的许多策略，总结了来自已完成和正在进行的临床试验的当代数据。本文描述的工作强调了细菌改变癌症治疗格局的潜力，将古老的智慧与现代科学创新联系起来。