Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy
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Abstract
Inosine modulates antitumor immunity Checkpoint blockade immunotherapy harnesses the immune system to kill cancer cells and has been used with great success to treat certain tumors, but not all cancer patients respond. The efficacy of checkpoint blockade immunotherapy has been shown to depend on the presence of distinct, beneficial bacteria residing in the gut of patients, but how the microbiome mediates such beneficial effects is unclear. Mager et al. found that specific bacteria produce a metabolite called inosine that enhances the effect of checkpoint blockade immunotherapy (see the Perspective by Shaikh and Sears). In mouse models, inosine, together with proinflammatory stimuli and immunotherapy, strongly enhanced the antitumor capacities of T cells in multiple tumor types, including colorectal cancer, bladder cancer, and melanoma. Science , this issue p. 1481 ; see also p. 1427
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The record
- Venue
- Science
- Topic
- Cancer Immunotherapy and Biomarkers
- Field
- Medicine
- Canadian institutions
- Centre Hospitalier de l’Université de MontréalAlberta Children's HospitalUniversity of Calgary
- Funders
- Natural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchAlberta InnovatesSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Keywords
- InosineImmunotherapyMicrobiomeComputational biologyChemistryBiologyImmunologyImmune systemBioinformaticsBiochemistryAdenosine
- Has abstract in OpenAlex
- yes