Prebiotics-induced anti-tumor immunity attenuates tumor growth

Growing evidence supports a key role of gut microbiota in tumor control and response to checkpoint inhibitor therapy. Yet, what underlies bacterial taxa enrichment, or its ability to induce anti-tumor phenotypes, remains unknown. Here we identify select prebiotics that enrich bacterial taxa that promote anti-tumor immunity. The addition of either inulin or mucin to normal diet of C57BL/6 mice induced anti-tumor immune responses with concomitant inhibition of BRAF mutant melanoma growth. When administered to germ free mice, mucin failed to inhibit tumor growth, pointing to the requirement of gut microbiota in the activation of anti-tumor immunity. Notably, inulin, but not mucin, limited the growth of colon cancer and of NRAS mutant melanomas, enhanced MEKi inhibition of melanoma growth, and delayed melanoma resistance to MEKi. While substantiating the importance of gut microbiota composition as a regulator of antitumor immunity, our findings point to the effectiveness of select prebiotics in this process.