Long-distance microbial mechanisms impacting cancer immunosurveillance.

The intestinal microbiota determines immune responses against extraintestinal antigens, including tumor-associated antigens. Indeed, depletion or gross perturbation of the microbiota undermines the efficacy of cancer immunotherapy, thereby compromising the clinical outcome of cancer patients. In this review, we discuss the long-distance effects of the gut microbiota and the mechanisms governing antitumor immunity, such as the translocation of intestinal microbes into tumors, migration of leukocyte populations from the gut to the rest of the body, including tumors, as well as immunomodulatory microbial products and metabolites. The relationship between these pathways is incompletely understood, in particular the significance of the tumor microbiota with respect to the identification of host and/or microbial products that regulate the egress of bacteria and immunocytes toward tumor beds. The intestinal microbiota influences cancer immunosurveillance in extraintestinal tumors via three potential mechanisms: (1) the gut-to-tumor translocation of microbes, (2) the migration of intestinal leukocytes toward the tumor microenvironment, and (3) extraintestinal effects of microbial products or metabolites. Zitvogel and Kroemer discuss the molecular bases of these long-distance effects. [ABSTRACT FROM AUTHOR]