Prevotella melaninogenica could be a promising strategy to treat smoldering multiple myeloma and to make immunotherapy

Intestinal microbiota and gut-born T helper 17 (Th17) lymphocytes may act as drivers of smoldering multiple myeloma (SMM) to MM evolution. We demonstrate here that administering the human commensal Prevotella melaninogenica (P.m.) to transgenic Vk*MYC mice affected by Early-MM, mimicking human SMM, significantly delayed evolution to full-blown MM. Mechanistically, P.m. induced increased production of short-chain fatty acids (SCFAs), preventing skew of dendritic cells towards a pro-Th17 phenotype and accumulation of Th17 cells in the bone marrow of mice affected by relapsing-remitting MM. P.m. or butyrate synergized with anti-PD-L1 antibodies by restraining Th17 cell expansion while unleashing immune checkpoint blockade (ICB)-induced effector CD8+ T cells, eventually blocking progression to MM. P.m. also ameliorated skin lesions mimicking immune-related adverse events caused by ICB. Thus, modulation of the gut microbiota or administration of SCFAs with or without ICB might represent treatment options for patients affected by plasma cell dyscrasias and other hematologic or solid tumors in which IL-17 acts as driving force.