Details

Autor(en) / Beteiligte

• Wang, Menglin
• Rousseau, Benoit
• Qiu, Kunyu
• Huang, Guannan
• Zhang, Yu
• Su, Hang
• Le Bihan-Benjamin, Christine
• Khati, Ines
• Artz, Oliver
• Foote, Michael B
• Cheng, Yung-Yi
• Lee, Kuo-Hsiung
• Miao, Michael Z
• Sun, Yue
• Bousquet, Philippe-Jean
• Hilmi, Marc
• Dumas, Elise
• Hamy, Anne-Sophie
• Reyal, Fabien
• Lin, Lin
• Armistead, Paul M
• Song, Wantong
• Vargason, Ava
• Arthur, Janelle C
• Liu, Yun
• Guo, Jianfeng
• Zhou, Xuefei
• Nguyen, Juliane
• He, Yongqun
• Ting, Jenny P-Y
• Anselmo, Aaron C
• Huang, Leaf

Titel

Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses

Ist Teil von

• Nature biotechnology, 2024-08, Vol.42 (8), p.1263-1274

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2024

Beschreibungen/Notizen

• 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.