Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses Journal Article
| Authors: | Wang, M.; Rousseau, B.; Qiu, K.; Huang, G.; Zhang, Y.; Su, H.; Le Bihan-Benjamin, C.; Khati, I.; Artz, O.; Foote, M. B.; Cheng, Y. Y.; Lee, K. H.; Miao, M. Z.; Sun, Y.; Bousquet, P. J.; Hilmi, M.; Dumas, E.; Hamy, A. S.; Reyal, F.; Lin, L.; Armistead, P. M.; Song, W.; Vargason, A.; Arthur, J. C.; Liu, Y.; Guo, J.; Zhou, X.; Nguyen, J.; He, Y.; Ting, J. P. Y.; Anselmo, A. C.; Huang, L. F. |
| Article Title: | Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses |
| Abstract: | 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. Killing bacteria in tumors boosts survival in a mouse model of colon cancer. |
| Keywords: | metabolism; peptide; resistance; colorectal-cancer; cells; mhc class-i; diversity; microbiome; fusobacterium-nucleatum; rna gene database |
| Journal Title: | Nature Biotechnology |
| Volume: | 42 |
| Issue: | 8 |
| ISSN: | 1087-0156 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-08-01 |
| Start Page: | 1263 |
| End Page: | 1274 |
| Language: | English |
| ACCESSION: | WOS:001070333900001 |
| DOI: | 10.1038/s41587-023-01957-8 |
| PROVIDER: | wos |
| PUBMED: | 37749267 |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF -- Source: Wos |
