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Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer

  1. Author:
    Dmitrieva-Posocco, Oxana
    Dzutsev, Amiran
    Posocco, David F
    Hou, Vivianty
    Yuan, Wuxing
    Thovarai, Vishal
    Mufazalov, Ilgiz A
    Gunzer, Matthias
    Shilovskiy, Igor P
    Khaitov, Musa R
    Trinchieri, Giorgio
    Waisman, Ari
    Grivennikov, Sergei I

  2. Author Address

    Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA; Personalized Medicine and Molecular Immunology, National Research Center - Institute of Immunology, FMBA, Moscow, 115478, Russia., Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA., Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, 55131, Germany., University Duisburg-Essen, University Hospital, Institute for Experimental Immunology and Imaging, 45122 Essen, Germany., Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA. Electronic address: sergey.grivennikov@fccc.edu.,
    1. Year: 2019
    2. Date: Jan 15
  2. Journal: Immunity
    1. 50
    2. 1
    3. Pages: 166-180.e7
  4. Type of Article: Article
  5. ISSN: 1074-7613
  1. Abstract:

    Chronic inflammation drives the progression of colorectal cancer (CRC). Increased expression of interleukin (IL)-17A is associated with poor prognosis, and IL-17A blockade curbs tumor progression in preclinical models of CRC. Here we examined the impact of IL-1 signaling, a key regulator of the IL-17 pathway, in different cell types within the CRC microenvironment. Genetic deletion of the IL-1 receptor (IL-1R1) in epithelial cells alleviated tumorigenesis in the APC model of CRC, demonstrating a cell-autonomous role for IL-1 signaling in early tumor seed outgrowth. T cell specific ablation of IL-1R1 decreased tumor-elicited inflammation dependent on IL-17 and IL-22, thereby reducing CRC progression. The pro-tumorigenic roles of IL-1 were counteracted by its effects on myeloid cells, particularly neutrophils, where IL-1R1 ablation resulted in bacterial invasion into tumors, heightened inflammation and aggressive CRC progression. Thus, IL-1 signaling elicits cell-type-specific responses, which, in aggregate, set the inflammatory tone of the tumor microenvironment and determine the propensity for disease progression. Copyright © 2018 Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.immuni.2018.11.015
  3. PMID: 30650375
  4. View record in Web of Science®
  5. WOS: 000455661600018
  6. PII : S1074-7613(18)30523-5

Library Notes

  1. Fiscal Year: FY2018-2019
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