Effect of TLR agonists on the differentiation and function of human monocytic myeloid-derived suppressor cells

Jing Wang, Yuko Shirota, Defne Bayik, Hidekazu Shirota, Debra Tross, James L. Gulley, Lauren V. Wood, Jay A. Berzofsky, Dennis M. Klinman

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Tumors persist by occupying immunosuppressive microenvironments that inhibit the activity of tumoricidal Tand NK cells. Monocytic myeloid-derived suppressor cells (mMDSC) are an important component of this immunosuppressive milieu. We find that the suppressive activity of mMDSC isolated from cancer patients can be reversed by treatment with TLR7/8 agonists, which induce human mMDSC to differentiate into tumoricidal M1-like macrophages. In contrast, agonists targeting TLR1/2 cause mMDSC to mature into immunosuppressive M2-like macrophages. These two populations of macrophage are phenotypically and functionally discrete and differ in gene expression profile. The ability of TLR7/8 agonists to reverse mMDSC-mediated immune suppression suggests that they might be useful adjuncts for tumor immunotherapy.

Original languageEnglish
Pages (from-to)4215-4221
Number of pages7
JournalJournal of Immunology
Volume194
Issue number9
DOIs
Publication statusPublished - 2015 May 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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