越来越多的证据表明肿瘤微生物群是影响癌症进展的一个因素。在结直肠癌 (CRC) 患者中，我们发现针对厌氧菌的切除前抗生素可显着提高 25.5% 的无病生存率。对于小鼠研究，我们设计了一种封装在脂质体中的抗生素银-替硝唑复合物（LipoAgTNZ），以消除原发肿瘤和肝转移瘤中的肿瘤相关细菌，而不引起肠道微生物群失调。被促肿瘤细菌（具核梭杆菌属）或益生菌（大肠杆菌尼氏菌属）定植的小鼠 CRC 模型对 LipoAgTNZ 治疗有反应，这使得两个感染具核梭杆菌的 CRC 模型的长期存活率超过 70%。抗生素治疗产生微生物新抗原，引发抗肿瘤 CD8 T 细胞。异源和同源细菌表位有助于免疫原性，启动 T 细胞识别感染和未感染的肿瘤。我们的策略针对肿瘤相关细菌，以引发抗肿瘤免疫，为微生物组免疫治疗干预措施铺平道路。© 2023。作者，获得 Springer Nature America, Inc. 的独家许可。

Increasing evidence implicates the tumor microbiota as a factor that can influence cancer progression. In patients with colorectal cancer (CRC), we found that pre-resection antibiotics targeting anaerobic bacteria substantially improved disease-free survival by 25.5%. For mouse studies, we designed an antibiotic silver-tinidazole complex encapsulated in liposomes (LipoAgTNZ) to eliminate tumor-associated bacteria in the primary tumor and liver metastases without causing gut microbiome dysbiosis. Mouse CRC models colonized by tumor-promoting bacteria (Fusobacterium nucleatum spp.) or probiotics (Escherichia coli Nissle spp.) responded to LipoAgTNZ therapy, which enabled more than 70% long-term survival in two F. nucleatum-infected CRC models. The antibiotic treatment generated microbial neoantigens that elicited anti-tumor CD8+ T cells. Heterologous and homologous bacterial epitopes contributed to the immunogenicity, priming T cells to recognize both infected and uninfected tumors. Our strategy targets tumor-associated bacteria to elicit anti-tumoral immunity, paving the way for microbiome-immunotherapy interventions.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.