Fig. 3
From: Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies
Potential mechanisms by which the gut microbial metabolite inosine facilitates the efficacy of ICI. Inosine, purine metabolite of gut microbiota A. muciniphila and B. pseudolongum, combined with in ICI therapy exert synergistic antitumor effects. A Inosine increases the immunogenicity of tumor cells. Inosine can improve the ability of tumor cells to present tumor antigens so that cytotoxic immune cells can easily recognize and kill tumor cells. B Inosine promotes immune cell activation. Inosine could enhance ICI efficacy by acting on A2AR on T lymphocytes. It stimulates the phosphorylation of cAMP response element-binding protein (pCREB) through the inosine-A2AR-cAMP-PKA signaling pathway, which can upregulate IL12Rβ2 and IFNγ transcription and promote Th1-cell differentiation and accumulation in the TME. C Inosine provides an alternative carbon source for CD8+ T cells. Inosine can be used as an alternative carbon source for CD8+ T cells when glucose is limited and relieves the restrictions on CD8+ T cells energy metabolism in tumor cells