Microbiome modulation uncouples efficacy and toxicity induced by immune checkpoint blockade in mouse multiple myeloma

Le résumé fourni par la source

Smoldering multiple myeloma (SMM), which is in principle curable, may develop into life-threatening MM. Intestinal microbiota and gut-born T helper-17 (Th17) lymphocytes may contribute to this development, but the mechanisms are unclear. Here we demonstrate that administering the human commensal Prevotella melaninogenica to transgenic Vk*MYC mice that exhibit SMM-like phenotypes delays the evolution to full-blown MM. Mechanistically, P. melaninogenica increases the production of short-chain fatty acids (SCFA), thereby preventing the skewing of dendritic cells towards a pro-Th17 phenotype and subsequently accumulation of Th17 cells in the bone marrow of treated mice. P. melaninogenica or butyrate synergizes with anti-PD-L1 or anti-TIGIT to suppress myeloma progression by restraining Th17 cell expansion while inducing effector CD8+ T cells. P. melaninogenica also attenuates IL-17-mediated skin lesions that mimic anti-PD-L1-induced adverse events. Our results thus suggest that gut microbiota modulation or SCFAs administration may represent treatment options for patients affected by plasma cell dyscrasias. Smoldering multiple myeloma (SMM) may develop into life- threatening MM, with gut microbiota and Th17 possibly contributing to this progression via unknown mechanisms. Here the authors use a mouse SMM model, VkMYC mice, to show that treatments with butyrate or the commensal, Prevotella melaninogenica, suppress Th17 and cancer progression.

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