Figure 2.

Systemic effects of the gut microbiota on antitumor immunity and immunotherapy. The gut microbiota could modulate immunotherapy outcomes by stimulating or inhibiting antitumor immunity. The messengers that could carry signals from the gut and/or gut-associated lymphoid tissues (GALT) to a distant tumor site include (1) bacterial metabolites that enter the circulation and regulate gene expression in various cells; (2) microbe-associated molecular patterns (MAMPs), which can modulate innate immunity by signaling through pattern recognition receptors, such as TLRs; (3) whole viable bacteria could potentially translocate and affect immune responses or drug activity in distant tumor tissues; (4) immune cells conditioned by sensing microbiota signals in the GALT could migrate and carry out immune-stimulatory or -inhibitory functions in distant tumors; and (5) cytokines could be released in the GALT in response to microbial stimuli and potentially enter the circulation and modulate downstream immune functions systemically. APC, antigen presenting cell; MDSC, myeloid-derived suppressor cell; MLN, mesenteric lymph node.