Figure 2.

The effect of intestinal microbes and their metabolites on the responses to cancer immunotherapy. Intestinal microbes can affect patients’ responses to immunotherapies through interaction with the host immune system. Alistipes putredinis, Bifidobacterium longum, and Prevotella copri can activate NK cells and memory CD8⁺ T cells and thus enhance the response to anti-PD-1 therapy. SCFAs strengthen the function of memory CD8⁺ T cells and foster their differentiation into TCF-1⁺ PD-1⁺ CD8⁺ T cells, thus improving the efficacy of anti-PD-1 treatment. Gut microbiota dysbiosis induced by antibiotics results in the poor response to immune checkpoint inhibitors. EPS-R1 can augment the anticancer effects of anti-CTLA-4 and anti-PD-1 treatments by inducing CCR6⁺ CD8⁺ T cells in Peyer’s patches and fostering their infiltration into CCL20-expressing tumors. Lactobacillus paracasei sh2020 promotes the infiltration of IFN-γ⁺ CD8⁺ T cells into tumor tissues by increasing the expression of T cell chemoattractant chemokines. Accordingly, L. paracasei sh2020 improves the response to anti-PD-1 therapy. Bifidobacteria enhances the efficacy of anti-CD47 therapy through activation of dendritic cells. SCFAs, short-chain fatty acids; EPS-R1, exopolysaccharide produced by Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1; PD-1, programmed death-1; CCR6, C-C motif chemokine receptor 6; IFN-γ, interferon-γ; TCF-1, T cell factor-1, NK cell, natural killer cell; PD-L1, programmed death-ligand 1; MHC-I, major histocompatibility complex class I; TCR, T cell receptor; CTLA-4, cytotoxic T lymphocyte-associated antigen-4; MHC-II, major histocompatibility complex class II; CXCL9, C-X-C motif chemokine ligand 9; CXCL10, C-X-C motif chemokine ligand 10; CXCL11, C-X-C motif chemokine ligand 11; IFNγR, interferon-γ receptor.