Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses
Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses
复制标题
用脂质体抗生素杀死肿瘤相关细菌会产生诱导抗肿瘤免疫反应的新抗原
DOI：
10.1038/s41587-023-01957-8
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发表时间：
2023-09-25
影响因子：
46.9
通讯作者：
Huang，Leaf
中科院分区：
文献类型：
--
作者：
Wang，Menglin;Rousseau，Benoit;Huang，Leaf
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 nucleatumspp.) or probiotics (Escherichia coliNissle spp.) responded to LipoAgTNZ therapy, which enabled more than 70% long-term survival in twoF. 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.
