Commensal Bacteria Control Cancer Response to Therapy by Modulating the Tumor Microenvironment

TLDR

The gut microbiota modulates local and systemic inflammation, which influences cancer development and treatment, yet it remains unclear how commensal bacteria affect inflammation within the sterile tumor microenvironment. Disrupting the microbiota in mice diminishes tumor responses to CpG immunotherapy and platinum chemotherapy by impairing myeloid‑derived cell functions, demonstrating that an intact commensal microbiota is essential for effective cancer treatment.

Abstract

The gut microbiota influences both local and systemic inflammation. Inflammation contributes to development, progression, and treatment of cancer, but it remains unclear whether commensal bacteria affect inflammation in the sterile tumor microenvironment. Here, we show that disruption of the microbiota impairs the response of subcutaneous tumors to CpG-oligonucleotide immunotherapy and platinum chemotherapy. In antibiotics-treated or germ-free mice, tumor-infiltrating myeloid-derived cells responded poorly to therapy, resulting in lower cytokine production and tumor necrosis after CpG-oligonucleotide treatment and deficient production of reactive oxygen species and cytotoxicity after chemotherapy. Thus, optimal responses to cancer therapy require an intact commensal microbiota that mediates its effects by modulating myeloid-derived cell functions in the tumor microenvironment. These findings underscore the importance of the microbiota in the outcome of disease treatment.