Mechanistic studies of modulation of immunotherapy effect by microbiota
| Immunotherapy | Involved microbes | Mechanisms |
| Anti-CTLA-4 mAbs | Bacteroides fragilis, Bacteroides thetaiotaomicron and Burkholderia cepacia | Stimulation of CD11b+ DCs improved IL-12–dependent Th1 immune response for enhanced antitumour immune response.93 |
| Bifidobacterium | Bifidobacterium enhanced the suppressive functions of Treg cells to minimise immunopathology induced by treatment.96 97 | |
| Bifidobacterium pseudolongum and Akkermansia muciniphila | Bacterial-derived inosine acted on adenosine 2A receptors to stimulate Th1 response in the presence of costimulations from DCs and enhanced tumour shrinkage.99 | |
| Anti-PD-1/PD-L1 mAbs | Bifidobacterium breve and Bifidobacterium longum |
Bifidobacterium activated DCs for CD8+ T cell priming and infiltration in the tumour microenvironment to enhance anticancer immune response of treatment.94
Bifidobacterium could also secrete hippurate and reduce PD-1 molecule expression to activate NK cells for anticancer effects.101 |
| Lactobacillus rhamnosus GG | LGG activated DCs via cGAS-STING-TBK1-IRF7-IFN-β cascade to enhance CD8+ T cell activity against tumour cells.102 | |
| Bifidobacterium breve | Molecular mimicry between SVY antigen of B. breve and SIY neoantigen of mouse melanoma stimulated cross-reactive T cell response against melanoma cells.105 | |
| Bacteriophage-infecting Enterococcus hirae | TMP of bacteriophage-infecting E. hirae stimulated memory CD8+ T cell cross-reaction with cancer antigen PSMB4 protein.106 |
cGAS, cyclic GMP-AMP synthase; CTLA-4, cytotoxic T lymphocyte-associated antigen-4; DCs, dendritic cells; IFN-β, interferon-β; IL, interleukin; IRF7, interferon regulatory factor 7; LGG, Lactobacillus rhamnosus GG; mAbs, monoclonal antibodies; NK, natural killer; PD-1, programmed cell death protein-1; PD-L1, programmed death-ligand 1; PSMB4, proteasome subunit beta type-4; SIY, SIYRYYGL; STING, stimulator of IFN genes; SVY, SVYRYYGL; TBK1, TANK binding kinase 1; Th, T helper; TMP, tape measure protein; Treg, T regulatory cells.