Abstract A02: Gut microbiome controls growth of liver tumors

Abstract

Aim: The gut microbiome can modify tumor immunity and has been suggested to be involved in the development and growth of liver cancer as well as metastasis in the liver. However, it remains unknown how the gut microbiome controls hepatic immune responses. This study was designed to exam the effect of the gut microbiome on liver antitumor immunity, and to study potential mechanism. Experimental Procedure: An antibiotic cocktail containing 0.5g/L vancomycin, 0.5 g/L neomycin and 0.6 g/L primaxin in drinking water was given to reduce mouse gut microbiota. Control mice were kept on regular water. EL4 thymoma cells were injected s.c. to induces spontaneous liver metastasis. B16 melanoma and CT26 colon cancer cells were injected intrasplenically to form liver metastasis. Lung metastasis was induced by tail injection of tumor cells. Spontaneous hepatocellular carcinomas were studied in TRE-MYC mice. Gut bacteria and metabolic studies were performed. Results: Antibiotic cocktail efficiently depleted gut bacteria. Removing gut commensal bacteria did not affect the growth of primary s.c. EL4 tumors, but impaired formation of liver metastasis in different models. The inhibitory effect on liver metastasis by removing gut microbiome was found after intrasplenic injection of tumor cells to form liver metastasis using both B16 melanoma and CT26 colon cancer tumor cells as well as in TRE-MYC mice. Interestingly, formation of lung metastasis caused by tail vein injection of B16 cells was not impaired by antibiotics treatment, suggesting a liver specific effect. The inhibition of liver metastasis by antibiotic treatment was absent in Rag1 knockout mice, suggesting that the observed mechanism is mediated by the adaptive immune system. A detailed mechanism how the gut microbiome causes metabolic liver changes and thereby growth of liver tumors will be presented. Conclusion: Our results suggest that the gut microbiome affects the liver immune microenvironment and modulates antitumor immunity Citation Format: Chi Ma, Miaojun Han, Bernd Heinrich, Qiong Fu, Qianfei Zhang, Xin W. Wang, Giorgio Trinchieri, Tim Greten. Gut microbiome controls growth of liver tumors [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A02.