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.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Bacterial Agents / administration & dosage
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Antigen Presentation / genetics
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Antineoplastic Agents / therapeutic use
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Bacteria / drug effects
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Bacterial Physiological Phenomena / drug effects
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Down-Regulation
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Gene Expression Regulation
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Germ-Free Life
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Immunotherapy
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Inflammation / genetics
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Intestines / microbiology*
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Melanoma, Experimental
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Mice
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Mice, Inbred C57BL
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Microbiota / drug effects
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Microbiota / physiology*
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Neoplasm Transplantation
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Neoplasms / immunology*
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Neoplasms / microbiology
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Neoplasms / therapy*
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Oligodeoxyribonucleotides / therapeutic use
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Organoplatinum Compounds / therapeutic use
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Oxaliplatin
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Phagocytosis / genetics
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Reactive Oxygen Species / metabolism
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Symbiosis
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Tumor Microenvironment / immunology*
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Anti-Bacterial Agents
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Antineoplastic Agents
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CPG-oligonucleotide
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Oligodeoxyribonucleotides
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Organoplatinum Compounds
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Reactive Oxygen Species
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Tumor Necrosis Factor-alpha
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Oxaliplatin