title: Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment.
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.
authors.affiliation: Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Noriho
authors.initials: N
authors.lastname: Iida
authors.forename: Amiran
authors.initials: A
authors.lastname: Dzutsev
authors.forename: C Andrew
authors.initials: CA
authors.lastname: Stewart
authors.forename: Loretta
authors.initials: L
authors.lastname: Smith
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bouladoux
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Weingarten
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Molina
authors.forename: Rosalba
authors.initials: R
authors.lastname: Salcedo
authors.forename: Timothy
authors.initials: T
authors.lastname: Back
authors.forename: Sarah
authors.initials: S
authors.lastname: Cramer
authors.forename: Ren-Ming
authors.initials: RM
authors.lastname: Dai
authors.forename: Hiu
authors.initials: H
authors.lastname: Kiu
authors.forename: Marco
authors.initials: M
authors.lastname: Cardone
authors.forename: Shruti
authors.initials: S
authors.lastname: Naik
authors.forename: Anil K
authors.initials: AK
authors.lastname: Patri
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Karen M
authors.initials: KM
authors.lastname: Frank
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.forename: Romina S
authors.initials: RS
authors.lastname: Goldszmid
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D017951:Antigen Presentation / Q000235:genetics; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects; D018407:Bacterial Physiological Phenomena / Q000187:drug effects; D015536:Down-Regulation; D005786:Gene Expression Regulation; D005856:Germ-Free Life; D007167:Immunotherapy; D007249:Inflammation / Q000235:genetics; D007422:Intestines / Q000382:microbiology*; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects / Q000502:physiology*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology* / Q000382:microbiology / Q000628:therapy*; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D010587:Phagocytosis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013559:Symbiosis; D059016:Tumor Microenvironment / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D009944:Organoplatinum Compounds; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000077150:Oxaliplatin