Fig. 2

The gut microbiota modulate innate immunity, adaptive immunity, and tumor antigens to improve ICI responses. A Innate immunity. DCs: Bifidobacterium, eleven strains and their metabolites, and Bacteroides fragilis promote DC maturation or activation and subsequent activation of CD8⁺ T cells and Th1 cells. NK cells: Lactobacillus plantarum increases NK cell activation; a high-salt diet increases intestinal permeability and localization of intratumoral Bifidobacterium and enhances NK cell activation to induce antitumor immunity. Monocyte: Feeding a high-fiber diet, monocolonization with cdAMP-producing A. muciniphila or transferring fecal microbiota from ICI responders can trigger the monocyte-IFN-I-NK-cell-DC cascade; Bifidobacterium facilitates CD47-based immunotherapy in a STING signaling and IFN-I-dependent fashion; Bacteroides fragilis induces macrophage phenotype polarization to M1. B Adaptive immunity. CD8⁺ T cells: Bifidobacterium, Enterococcus, Faecalibacterium, Ruminococcus, and Clostridiales promote CD8⁺ T cell infiltrates in tumor tissues; Phyla Firmicutes and Actinobacteria improve the activation of CD56⁺CD8⁺ T cells in the peripheral blood of ICI responders; and eleven strains increase the proportion of effector IFNγ⁺CD8⁺ T cells in the systemic circulation. CD4⁺ T cells: B. pseudolongum and Bacteroides fragilis stimulate Th1 immune responses; A. muciniphila triggers CCR9⁺CXCR3⁺CD4⁺ T lymphocyte recruitment into tumor beds; and Faecalibacterium increases the CD4⁺ T cell proportion. C Tumor cross-antigen. The gut microbiota increase the immunogenicity of tumor cells by providing tumor cross-antigens to ameliorate the efficacy of ICIs, including the antigen epitope TMP1 and the antigen epitope SVY