IL-1β regulates a novel myeloid-derived suppressor cell subset that impairs NK cell development and function

Moshe Elkabets, Vera S.G. Ribeiro, Charles A. Dinarello, Suzanne Ostrand-Rosenberg, James P. Di Santo, Ron N. Apte, Christian A.J. Vosshenrich

Research output: Contribution to journalArticlepeer-review

261 Scopus citations

Abstract

Chronic inflammation is associated with promotion of malignancy and tumor progression. Many tumors enhance the accumulation of myeloid-derived suppressor cells (MDSC), which contribute to tumor progression and growth by suppressing anti-tumor immune responses. Tumor-derived IL-1β secreted into the tumor microenvironment has been shown to induce the accumulation of MDSC possessing an enhanced capacity to suppress T cells. In this study, we found that the enhanced suppressive potential of IL-1β-induced MDSC was due to the activity of a novel subset of MDSC lacking Ly6C expression. This subset was present at low frequency in tumor-bearing mice in the absence of IL-1β-induced inflammation; however, under inflammatory conditions, Ly6Cneg MDSC were predominant. Ly6Cneg MDSC impaired NK cell development and functions in vitro and in vivo. These results identify a novel IL-1β-induced subset of MDSC with unique functional properties. Ly6Cneg MDSC mediating NK cell suppression may thus represent useful targets for therapeutic interventions.

Original languageEnglish
Pages (from-to)3347-3357
Number of pages11
JournalEuropean Journal of Immunology
Volume40
Issue number12
DOIs
StatePublished - 1 Dec 2010

Keywords

  • Cellular immunology
  • NK cells
  • Tumor immunology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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