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Fig. 2 | Cell Communication and Signaling

Fig. 2

From: Intestinal microbiota: a new force in cancer immunotherapy

Fig. 2

The regulation of the microbiota in adaptive immunity. Bacteroides fragilis stimulates TLR2 on CD4+ T cells by producing polysaccharide A (PSA), thereby enhancing the expression of Forkhead Box P3 (Foxp3), IL-10, and TGF-β. Butyrate activates Foxp3 via a G protein-coupled receptor (GPCR), induces differentiation of Tregs, and inhibits anti-tumor immune responses. Butyrate also indirectly promotes Treg differentiation by inducing IECs to secrete TGF-β. High concentrations of TGF-β inhibit the expression of IL-23R and promote the differentiation of Tregs. TGF-β also induces RORγt to be expressed together with Foxp3 in CD4+ T cells, which in turn inhibits RORγt, leading to differentiation of Tregs. Microbial metabolites SCFA and PSA can promote the proliferation of induced regulatory T cells (iTregs); however, too many iTregs infiltrating tumor tissue will weaken cancer immunity. PD-L1 can also promote the conversion of Tregs to iTregs by increasing the expression of Foxp3 and PTEN, or by inhibiting the Akt/mTOR pathway

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