Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment

Noriho Iida, Amiran Dzutsev, C. Andrew Stewart, Loretta Smith, Nicolas Bouladoux, Rebecca A. Weingarten, Daniel A. Molina, Rosalba Salcedo, Timothy Back, Sarah Cramer, Ren Ming Dai, Hiu Kiu, Marco Cardone, Shruti Naik, Anil K. Patri, Ena Wang, Francesco M. Marincola, Karen M. Frank, Yasmine Belkaid, Giorgio Trinchieri & 1 others Romina S. Goldszmid

Research output: Contribution to journalArticle

562 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)967-970
Number of pages4
JournalScience
Volume342
Issue number6161
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Tumor Microenvironment
Microbiota
Bacteria
Myeloid Cells
Neoplasms
Inflammation
Oligonucleotides
Therapeutics
Drug Therapy
Platinum
Immunotherapy
Reactive Oxygen Species
Necrosis
Cytokines
Anti-Bacterial Agents

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Iida, N., Dzutsev, A., Stewart, C. A., Smith, L., Bouladoux, N., Weingarten, R. A., ... Goldszmid, R. S. (2013). Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science, 342(6161), 967-970. https://doi.org/10.1126/science.1240527

Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. / Iida, Noriho; Dzutsev, Amiran; Stewart, C. Andrew; Smith, Loretta; Bouladoux, Nicolas; Weingarten, Rebecca A.; Molina, Daniel A.; Salcedo, Rosalba; Back, Timothy; Cramer, Sarah; Dai, Ren Ming; Kiu, Hiu; Cardone, Marco; Naik, Shruti; Patri, Anil K.; Wang, Ena; Marincola, Francesco M.; Frank, Karen M.; Belkaid, Yasmine; Trinchieri, Giorgio; Goldszmid, Romina S.

In: Science, Vol. 342, No. 6161, 2013, p. 967-970.

Research output: Contribution to journalArticle

Iida, N, Dzutsev, A, Stewart, CA, Smith, L, Bouladoux, N, Weingarten, RA, Molina, DA, Salcedo, R, Back, T, Cramer, S, Dai, RM, Kiu, H, Cardone, M, Naik, S, Patri, AK, Wang, E, Marincola, FM, Frank, KM, Belkaid, Y, Trinchieri, G & Goldszmid, RS 2013, 'Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment', Science, vol. 342, no. 6161, pp. 967-970. https://doi.org/10.1126/science.1240527
Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N, Weingarten RA et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 2013;342(6161):967-970. https://doi.org/10.1126/science.1240527
Iida, Noriho ; Dzutsev, Amiran ; Stewart, C. Andrew ; Smith, Loretta ; Bouladoux, Nicolas ; Weingarten, Rebecca A. ; Molina, Daniel A. ; Salcedo, Rosalba ; Back, Timothy ; Cramer, Sarah ; Dai, Ren Ming ; Kiu, Hiu ; Cardone, Marco ; Naik, Shruti ; Patri, Anil K. ; Wang, Ena ; Marincola, Francesco M. ; Frank, Karen M. ; Belkaid, Yasmine ; Trinchieri, Giorgio ; Goldszmid, Romina S. / Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. In: Science. 2013 ; Vol. 342, No. 6161. pp. 967-970.
@article{08d5e6a6b2d643ee9d2388abec53196c,
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.",
author = "Noriho Iida and Amiran Dzutsev and Stewart, {C. Andrew} and Loretta Smith and Nicolas Bouladoux and Weingarten, {Rebecca A.} and Molina, {Daniel A.} and Rosalba Salcedo and Timothy Back and Sarah Cramer and Dai, {Ren Ming} and Hiu Kiu and Marco Cardone and Shruti Naik and Patri, {Anil K.} and Ena Wang and Marincola, {Francesco M.} and Frank, {Karen M.} and Yasmine Belkaid and Giorgio Trinchieri and Goldszmid, {Romina S.}",
year = "2013",
doi = "10.1126/science.1240527",
language = "English",
volume = "342",
pages = "967--970",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6161",

}

TY - JOUR

T1 - Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment

AU - Iida, Noriho

AU - Dzutsev, Amiran

AU - Stewart, C. Andrew

AU - Smith, Loretta

AU - Bouladoux, Nicolas

AU - Weingarten, Rebecca A.

AU - Molina, Daniel A.

AU - Salcedo, Rosalba

AU - Back, Timothy

AU - Cramer, Sarah

AU - Dai, Ren Ming

AU - Kiu, Hiu

AU - Cardone, Marco

AU - Naik, Shruti

AU - Patri, Anil K.

AU - Wang, Ena

AU - Marincola, Francesco M.

AU - Frank, Karen M.

AU - Belkaid, Yasmine

AU - Trinchieri, Giorgio

AU - Goldszmid, Romina S.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84888049920&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888049920&partnerID=8YFLogxK

U2 - 10.1126/science.1240527

DO - 10.1126/science.1240527

M3 - Article

VL - 342

SP - 967

EP - 970

JO - Science

JF - Science

SN - 0036-8075

IS - 6161

ER -