Microbiota Modulation of Myeloid Cells in Cancer Therapy

摘要

Abstract Myeloid cells represent a major component of the tumor micro-environment, where they play divergent dual roles. They can induce antitumor immune responses, but mostly they promote immune evasion, tumor progression, and metastasis formation. Thus, strategies aiming at reprogramming the tumor microenvi-ronment represent a promising immunotherapy approach. Myeloid cells respond to environmental factors including signals derived from commensal microbes. In this Cancer Immunology at the Crossroads overview, we discuss recent advances on the effects of the commensal microbiota on myeloid-cell functions and how they affect the response to cancer therapy. The Microbiota Modulates Inflammation and Immunity by Priming Myeloid-Cell Differentiation and Functions Commensal microorganisms are abundant on all our epithelial barrier surfaces, where, directly or through released molecules, they interact with innate receptors and cytoplasmic sensors, thus regulating the development, tone, and maintenance of local inflammation and immunity (1). The interplay between the host immune system and the microbiota prevents tissue-damaging inflammatory responses to the commensals and controls the growth of indigenous pathobionts while it sets the stage for immune responses against pathogenic infections (2-4). This homeostatic immune regulation may be disrupted by changes in the microbial community that alter the symbiotic relationship with the microbiota, and the resultant microbial imbalance is commonly referred to asdysbiosis (5). Many regulatory mechanisms involved in these local interactions have been elucidated (6). In addition to local immunity, the commensal microbiota regulates systemic inflammation, innate resistance, and adaptive immunity, affecting both resistance to infection and autoimmu-nity (7-12). Maturation of the immune system is dependent on exposure to the microbiota following birth (13).