Literature DB >> 25533336

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

Melanie R Rutkowski1, Tom L Stephen1, Nikolaos Svoronos1, Michael J Allegrezza1, Amelia J Tesone1, Alfredo Perales-Puchalt1, Eva Brencicova1, Ximena Escovar-Fadul1, Jenny M Nguyen1, Mark G Cadungog2, Rugang Zhang3, Mariana Salatino4, Julia Tchou5, Gabriel A Rabinovich6, Jose R Conejo-Garcia7.   

Abstract

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.
Copyright © 2015 Elsevier Inc. All rights reserved.

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Year:  2014        PMID： 25533336      PMCID： PMC4293269          DOI： 10.1016/j.ccell.2014.11.009

Source DB:  PubMed          Journal:  Cancer Cell        ISSN： 1535-6108            Impact factor:   31.743


  26 in total

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Review 2.  Toll-like receptor polymorphisms and susceptibility to human disease.

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Authors:  Melanie R Rutkowski; Michael J Allegrezza; Nikolaos Svoronos; Amelia J Tesone; Tom L Stephen; Alfredo Perales-Puchalt; Jenny Nguyen; Paul J Zhang; Steven N Fiering; Julia Tchou; Jose R Conejo-Garcia
Journal:  J Vis Exp       Date:  2014-03-26       Impact factor: 1.355
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  107 in total

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4.  Exosomes Produced by Mesenchymal Stem Cells Drive Differentiation of Myeloid Cells into Immunosuppressive M2-Polarized Macrophages in Breast Cancer.

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8.  The Unfolded Protein Response Mediator PERK Governs Myeloid Cell-Driven Immunosuppression in Tumors through Inhibition of STING Signaling.

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9.  Tumor Cell-Independent Estrogen Signaling Drives Disease Progression through Mobilization of Myeloid-Derived Suppressor Cells.

Authors:  Nikolaos Svoronos; Alfredo Perales-Puchalt; Michael J Allegrezza; Melanie R Rutkowski; Kyle K Payne; Amelia J Tesone; Jenny M Nguyen; Tyler J Curiel; Mark G Cadungog; Sunil Singhal; Evgeniy B Eruslanov; Paul Zhang; Julia Tchou; Rugang Zhang; Jose R Conejo-Garcia
Journal:  Cancer Discov       Date:  2016-09-30       Impact factor: 39.397

10.  The human tumor microbiome is composed of tumor type-specific intracellular bacteria.

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