title: Interferon-γ and Tumor Necrosis Factor-α Polarize Bone Marrow Stromal Cells Uniformly to a Th1 Phenotype.
abstract: Activated T cells polarize mesenchymal stromal cells (MSCs) to a proinflammatory Th1 phenotype which likely has an important role in amplifying the immune response in the tumor microenvironment. We investigated the role of interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α), two factors produced by activated T cells, in MSC polarization. Gene expression and culture supernatant analysis showed that TNF-α and IFN-γ stimulated MSCs expressed distinct sets of proinflammatory factors. The combination of IFN-γ and TNF-α was synergistic and induced a transcriptome most similar to that found in MSCs stimulated with activated T cells and similar to that found in the inflamed tumor microenvironment; a Th1 phenotype with the expression of the immunosuppressive factors IL-4, IL-10, CD274/PD-L1 and indoleamine 2,3 dioxygenase (IDO). Single cell qRT-PCR analysis showed that the combination of IFN-γ and TNF-α polarized uniformly to this phenotype. The combination of IFN-γ and TNF-α results in the synergist uniform polarization of MSCs toward a primarily Th1 phenotype. The stimulation of MSCs by IFN-γ and TNF-α released from activated tumor infiltrating T cells is likely responsible for the production of many factors that characterize the tumor microenvironment.
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892 USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Jin
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892 USA.
authors.forename: Yuanlong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892 USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Jinguo
authors.initials: J
authors.lastname: Chen
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892 USA.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Ren
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892 USA.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Jin
authors.affiliation: Research Branch, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Davide
authors.initials: D
authors.lastname: Bedognetti
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892 USA.
authors.forename: Shutong
authors.initials: S
authors.lastname: Liu
authors.affiliation: Research Branch, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.affiliation: Research Branch, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Francesco
authors.initials: F
authors.lastname: Marincola
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892 USA.
authors.forename: David
authors.initials: D
authors.lastname: Stroncek
mesh_terms: D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D059010:Single-Cell Analysis; D018417:Th1 Cells; D059467:Transcriptome / Q000187:drug effects*; D059016:Tumor Microenvironment; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma