Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy

In this study, we isolated three bacterial species—Bifidobacterium pseudolongum, Lactobacillus johnsonii, and Olsenella species—that significantly enhanced efficacy of immune checkpoint inhibitors in four mouse models of cancer. We found that intestinal B. pseudolongum modulated enhanced immunotherapy response through production of the metabolite inosine. Decreased gut barrier function induced by immunotherapy increased systemic translocation of inosine and activated antitumor T cells. The effect of inosine was dependent on T cell expression of the adenosine A2A receptor and required costimulation. Collectively, our study identifies a previously unknown microbial metabolite immune pathway activated by immunotherapy that may be exploited to develop microbial-based adjuvant therapies.
Source: ScienceNOW - Category: Science Authors: Tags: Immunology, Medicine, Diseases reports Source Type: news