Interplay of gut microbiota, immune cells and natural products in reshaping cancer immunotherapy.

Recent advances have underscored the gut microbiota as an essential orchestrator of host responses to cancer immunotherapy. Gut microbiota and their metabolites play a vital role in modulating host immune responses. They regulate the development, differentiation, and function of a variety of immune cells, including granulocytes, monocytes, macrophages, dendritic cells (DCs), natural killer (NK) cells, innate lymphoid cells (ILCs), cytotoxic T cells (CTLs), helper T (Th) cells, regulatory T cells (Tregs), and B cells, as well as the production of cytokines such as interleukins (ILs), interferons (IFNs), tumor necrosis factors (TNFs), colony-stimulating factors (CSFs), chemokines, and growth factors (GFs). These cells and molecules are key mediators in shaping immune system. Natural products from meals, herbs, and microbial, plant, or fungal sources act as powerful modulators of gut microbiota. They can reshape microbial composition, regulate microbial metabolites and maintain intestinal barrier integrity. However, the interaction of natural products, gut microbiota, cytokines, and immune cells in modifying cancer immunotherapy is highly complex and remains largely unexplored. In this review, we summarize recent advances in understanding how natural products, microbiota, cytokines, and immune cells orchestrate to reshape the tumor microenvironment, offering novel insights and therapeutic opportunities for improving cancer immunotherapy.