Li et al. used syngeneic tumor models to show prebiotic (inulin and mucin)-mediated changes in gut microbiota, which correlated with stimulation of antitumor immunity and reduction in tumor growth. Inulin and mucin supplementation led to model-dependent enhanced immunoregulatory gene expression and infiltration of effector T cells and dendritic cells. When combined with a MEK inhibitor, inulin, but not mucin, delayed the emergence of resistance in N-Ras mutant melanoma. Inulin and mucin combination showed a synergistic antitumor effect in SW1 NRAS but not YUMM1.5 BRAF mutant melanoma tumors and did not synergize with anti-PD-1.
Contributed by Shishir Pant
ABSTRACT: Growing evidence supports the importance of gut microbiota in the control of tumor growth and response to therapy. Here, we select prebiotics that can enrich bacterial taxa that promote anti-tumor immunity. Addition of the prebiotics inulin or mucin to the diet of C57BL/6 mice induces anti-tumor immune responses and inhibition of BRAF mutant melanoma growth in a subcutaneously implanted syngeneic mouse model. Mucin fails to inhibit tumor growth in germ-free mice, indicating that the gut microbiota is required for the activation of the anti-tumor immune response. Inulin and mucin drive distinct changes in the microbiota, as inulin, but not mucin, limits tumor growth in synge-neic mouse models of colon cancer and NRAS mutant melanoma and enhances the efficacy of a MEK inhibitor against melanoma while delaying the emergence of drug resistance. We highlight the importance of gut microbiota in anti-tumor immunity and the potential therapeutic role for prebiotics in this process.
Author Info: (1) Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; (2) Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE 68588, U
Author Info: (1) Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; (2) Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA; (3) Technion Integrated Cancer Center, Faculty of Medicine, Technion, Haifa 3525433, Israel; (4) Present address: Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA; (5) These authors contributed equally; (6) Lead Contact *Correspondence: speterson@sbpdiscovery.org (S.N.P.), zeev@ronailab.net (Z.A.R.)
