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Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation.

Publication ,  Journal Article
Rutkowski, MR; Stephen, TL; Svoronos, N; Allegrezza, MJ; Tesone, AJ; Perales-Puchalt, A; Brencicova, E; Escovar-Fadul, X; Nguyen, JM; Zhang, R ...
Published in: Cancer Cell
January 12, 2015

The dominant TLR5(R392X) polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at extramucosal locations by increasing systemic IL-6, which drives mobilization of myeloid-derived suppressor cells (MDSCs). Mechanistically, expanded granulocytic MDSCs cause γδ lymphocytes in TLR5-responsive tumors to secrete galectin-1, dampening antitumor immunity and accelerating malignant progression. In contrast, IL-17 is consistently upregulated in TLR5-unresponsive tumor-bearing mice but only accelerates malignant progression in IL-6-unresponsive tumors. Importantly, depletion of commensal bacteria abrogates TLR5-dependent differences in tumor growth. Contrasting differences in inflammatory cytokines and malignant evolution are recapitulated in TLR5-responsive/unresponsive ovarian and breast cancer patients. Therefore, inflammation, antitumor immunity, and the clinical outcome of cancer patients are influenced by a common TLR5 polymorphism.

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Published In

Cancer Cell

DOI

EISSN

1878-3686

Publication Date

January 12, 2015

Volume

27

Issue

1

Start / End Page

27 / 40

Location

United States

Related Subject Headings

  • Toll-Like Receptor 5
  • Signal Transduction
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplasms
  • Neoplasm Transplantation
  • Molecular Sequence Data
  • Microbiota
  • Mice, Transgenic
  • Mice, Inbred C57BL
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rutkowski, M. R., Stephen, T. L., Svoronos, N., Allegrezza, M. J., Tesone, A. J., Perales-Puchalt, A., … Conejo-Garcia, J. R. (2015). Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation. Cancer Cell, 27(1), 27–40. https://doi.org/10.1016/j.ccell.2014.11.009
Rutkowski, Melanie R., Tom L. Stephen, Nikolaos Svoronos, Michael J. Allegrezza, Amelia J. Tesone, Alfredo Perales-Puchalt, Eva Brencicova, et al. “Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation.Cancer Cell 27, no. 1 (January 12, 2015): 27–40. https://doi.org/10.1016/j.ccell.2014.11.009.
Rutkowski MR, Stephen TL, Svoronos N, Allegrezza MJ, Tesone AJ, Perales-Puchalt A, et al. Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation. Cancer Cell. 2015 Jan 12;27(1):27–40.
Rutkowski, Melanie R., et al. “Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation.Cancer Cell, vol. 27, no. 1, Jan. 2015, pp. 27–40. Pubmed, doi:10.1016/j.ccell.2014.11.009.
Rutkowski MR, Stephen TL, Svoronos N, Allegrezza MJ, Tesone AJ, Perales-Puchalt A, Brencicova E, Escovar-Fadul X, Nguyen JM, Cadungog MG, Zhang R, Salatino M, Tchou J, Rabinovich GA, Conejo-Garcia JR. Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation. Cancer Cell. 2015 Jan 12;27(1):27–40.
Journal cover image

Published In

Cancer Cell

DOI

EISSN

1878-3686

Publication Date

January 12, 2015

Volume

27

Issue

1

Start / End Page

27 / 40

Location

United States

Related Subject Headings

  • Toll-Like Receptor 5
  • Signal Transduction
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplasms
  • Neoplasm Transplantation
  • Molecular Sequence Data
  • Microbiota
  • Mice, Transgenic
  • Mice, Inbred C57BL