Inosine: novel microbiota-derived immunostimulatory metabolite
In a recent paper published in Science, Mager et al.identify inosine as a metabolite produced by Bifidobacterium pseudolongum that improves the efficacy of anticancer immunotherapy in mice.Inosine produced in the gut reaches adenosine A2A receptors of T lymphocytes infiltrating tumors;thus, inosine joins an expanding list of immunostimulatory metabolites produced in the gut.The immune system loses its capacity to control tumor growth in conditions of gut dysbiosis, a microbial imbalance characterized by a rarefied ecological diversity with reduction of beneficial commensals and, in some cases, an overabundance of potentially harmful species.Thus, the presence of specific bacterial species in the intestinal lumen is required for immunotherapy targeting CTLA-4 or PD-1 to reduce tumor growth, as this has been shown in preclinical experiments involving germ-free mice or specific pathogen-free mice sterilized with broad-spectrum antibiotics,followed by recolonization of the gut with defined microbial strains.1-4 Mechanistically, it appears that specific species in the microbiota can provide co-stimulatory signals acting on pattern recognition receptors to facilitate immune activation in the form of ”co-stimuli”,s generate immunostimulatory metabolites (such a polyamines and vitamins B3 or B6)6,7 or provide antigens that cross-react with tumor-associated antigens, thus boosting the recognition and destruction of malignant cells by cytotoxic T lymphocytes.8
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2020-12-07（万方平台首次上网日期，不代表论文的发表时间）
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942-943
