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Comment
. 2020 Nov;30(11):942-943.
doi: 10.1038/s41422-020-00417-1.

Inosine: novel microbiota-derived immunostimulatory metabolite (VSports在线直播)

Guido Kroemer  1   2   3   4   5 , Laurence Zitvogel  6   7   8   9   10
Affiliations
Comment

Inosine: novel microbiota-derived immunostimulatory metabolite

Guido Kroemer (V体育ios版) et al. Cell Res. 2020 Nov.
No abstract available

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Conflict of interest statement

G. K. and L VSports手机版. Z. are scientific co-founders of everImmune.

Figures

Fig. 1
Fig. 1. Inosine/adenosine receptor A2-dependent co-stimulation of pro-Th1 and pro-Tc1 cells is required for the immunostimulatory effect of gut-resident B. pseudolongum in colon cancer immunotherapy.
During immunotherapy with the immune checkpoint inhibitor (ICI) anti-CTLA-4 (combined with either CpG or anti-PDL-1 antibody), inosine produced by gut-resident microbial species (such as B. pseudolongum and A. muciniphila) in a descending gradient from the duodenum to the ileum leads to A2AR-dependent costimulatory effects on T cells, Th1/Tc1 differentiation and accumulation in tumor beds (DSS-AOM colon cancer, subcutaneous MC38 colon cancer or Msh2LoxP/LoxPVillin-Cre model). Indeed, A2AR signaling in T lymphocytes is mandatory for the immunotherapy-promoting effects of B. pseudolongum and allows for upregulation of IL12Rβ2 and IFNγ transcription, while IL-12 is secreted by cDC1 in contact with bacteria including B. pseudolongum, likely in secondary lymphoid organs. pCREB, phosphorylation of cAMP response element-binding protein; mLN, mesenteric lymph node; LP, lamina propria; MSI, microsatellite instable; MSS, microsatellite stable; ip, intraperitoneally; iv, intravenously; DTR, diphteria toxin receptor; per os, orally.
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References

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    1. Zitvogel L, et al. Science. 2018;359:1366–1370. - PubMed (V体育平台登录)

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