Oncolytic bacteria can trigger innate immune activity. However, the antitumour efficacy of inactivated bacteria is poor, and attenuated live bacteria pose substantial safety risks. Here we show that intratumourally injected paraformaldehyde-fixed bacteria coated with manganese dioxide potently activate innate immune activity, modulate the immunosuppressive tumour microenvironment and trigger tumour-specific immune responses and abscopal antitumour responses. A single intratumoural administration of mineralized Salmonella typhimurium suppressed the growth of multiple types of subcutaneous and orthotopic tumours in mice, rabbits and tree shrews and protected the cured animals against tumour rechallenge. We also show that mineralized bacteria can be administered via arterial embolization to treat orthotopic liver cancer in rabbits. Our findings support the further translational testing of oncolytic mineralized bacteria as potent and safe antitumour immunotherapeutics.

溶瘤细菌可以触发先天免疫活动。但灭活菌的抗肿瘤功效较差，减毒活菌存在较大的安全风险。在这里，我们表明，肿瘤内注射多聚甲醛固定的涂有二氧化锰的细菌可有效激活先天免疫活性，调节免疫抑制性肿瘤微环境并触发肿瘤特异性免疫反应和远隔抗肿瘤反应。矿化鼠伤寒沙门氏菌的单次肿瘤内给药抑制了小鼠、兔子和树鼩体内多种类型的皮下和原位肿瘤的生长，并保护治愈的动物免受肿瘤的再次攻击。我们还表明，可以通过动脉栓塞施用矿化细菌来治疗兔子的原位肝癌。我们的研究结果支持将溶瘤矿化细菌作为有效且安全的抗肿瘤免疫治疗剂进行进一步的转化测试。