title: Effect of TLR agonists on the differentiation and function of human monocytic myeloid-derived suppressor cells.
abstract: Tumors persist by occupying immunosuppressive microenvironments that inhibit the activity of tumoricidal T and 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.
authors.affiliation: Cancer and Inflammation Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702;
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Cancer and Inflammation Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702;
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shirota
authors.affiliation: Cancer and Inflammation Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702;
authors.forename: Defne
authors.initials: D
authors.lastname: Bayik
authors.affiliation: Cancer and Inflammation Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702;
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Shirota
authors.affiliation: Cancer and Inflammation Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702;
authors.forename: Debra
authors.initials: D
authors.lastname: Tross
authors.affiliation: Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD 20892; and.
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
authors.forename: Lauren V
authors.initials: LV
authors.lastname: Wood
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
authors.affiliation: Cancer and Inflammation Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702; klinmand@mail.nih.gov.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D022423:Myeloid Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D013329:Structure-Activity Relationship; D051193:Toll-Like Receptors / Q000819:agonists* / Q000276:immunology
chemical_list: D007093:Imidazoles; D051193:Toll-Like Receptors; C402365:resiquimod
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