B. animalis-derived mannose enhances anti-PD-1 efficacy in melanoma by inhibiting YAP1 in CD8+ T cells. (IMAGE)
Caption
B. animalis-derived mannose enhances anti-PD-1 efficacy in melanoma by inhibiting YAP1 in CD8+ T cells. In Part 1, a human-faeces B. animalis isolate is shown to suppress B16-F10 tumors in vitro and in vivo, concomitantly re-programming the TIME. Part 2 identifies mannose as the key < 3-kDa immunostimulatory metabolite derived from B. animalis that activates CD8+ T cells and enhances anti-PD-1 efficacy. Part 3 shows that mannose triggers CD8+ T cell-dependent anti-tumor effects by downregulating YAP1, thereby releasing the Hippo brake on cytotoxicity. Collectively, these findings reveal a novel microbiota–metabolite–immune axis wherein B. animalis-derived mannose potentiates anti-PD-1 therapy via YAP1 suppression in CD8+ T cells. Abbreviations: B. animalis, Bifidobacterium animalis, Ba.CM, B. animalis conditioned medium; CM, conditioned medium; ICIs, immune checkpoint inhibitors; TIME, tumor immune microenvironment. Figure created using BioRender (www.biorender.com).
Credit
Cancer Biology & Medicine
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