New Paper: Microbiome-Derived Inosine Modulates Response to Checkpoint Inhibitor Immunotherapy

Congratulations to our Director and Platform 1 Lead Dr. Kathy McCoy, as well as our Platform 4 Co-Lead Dr. Ian Lewis and our Education & Mentorship Lead Dr. Markus Geuking, on this recent publication!

Using an interdisciplinary approach, the authors identified three bacterial species that significantly enhanced the efficacy of immune checkpoint inhibitors in four mouse models of cancer! This promising study” identifies a novel microbial metabolite-immune pathway that may be exploited to develop microbial-based adjuvant therapies.”

Lukas Mager and Kathy McCoy have discovered how bacteria within our microbiome can help battle some forms of cancer. Photograph: Kelly Johnston, Cumming School of Medicine

Abstract

Several species of intestinal bacteria have been associated with enhanced efficacy of checkpoint blockade immunotherapy, but the underlying mechanisms by which the microbiome enhances anti-tumor immunity is unclear. Here, we isolated three bacterial species, including Bifidobacterium pseudolongumLactobacillus 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 anti-tumor T cells. The effect of inosine was dependent on T cell expression of the adenosine A2A receptor and required co-stimulation. Collectively, our study identifies a novel microbial metabolite-immune pathway that is activated by immunotherapy that may be exploited to develop microbial-based adjuvant therapies.

Read more in the press release and discover the research behind this promising discovery!

Publication: Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy. Mager LF, Burkhard R, Pett N, Cooke NCA, Brown K, Ramay H, Paik S, Stagg J, Groves RA, Gallo M, Lewis IA, Geuking MB, McCoy KD. Science. 18 September 2020.