Figure 2.

Potential mechanism that explains the anticancer or pro-cancer effects of some candidate ICI-therapy-associated bacteria by shaping the host immune status. Lactobacilli may upregulate the expression of MHC-II on DCs, enhance the activity of NK cells and macrophages, and improve Th1-mediated immune responses as well as increase the production of IFN-γ in tumors. The effects described above facilitate the anticancer potential of Lactobacilli. Bifidobacteria can improve the efficacy of anti-PD-L1 therapy by upregulating the expression of MHC-II on DCs, promoting Th1 polarization and CTL accumulation in the tumor microenvironments, and reducing the toxicity of anti-CTLA-4 therapy through enhanced Treg cell metabolism. Akkermansia muciniphila can enhance the efficacy of anti-PD-1 therapy in a manner dependent on the enhanced IL-12-dependent Th1-related immune response, along with increased levels of IFN-γ and TNF-α and decreased levels of IL-4 and IL-10. The results from a preclinical trial confirmed that Bacteroidetes can restore anti-CTLA-4 treatment efficacy by enhancing the IL-12-dependent Th1-related immune response, whereas these bacteria are associated with poor clinical outcomes of anti-CTLA-4 or anti-PD-1 therapy in human clinical trials. Fusobacterium nucleatum can promote tumor progression in gastrointestinal cancer and pancreatic cancer, and it is verified to be associated with reduced density of CD3 + T cells, exhaustion of NK cells, and augmentation of M2 polarization along with accumulation of MDSCs in tumor microenvironments. These effects may be closely linked with their colonization in tumors.