Interferon-γ and Tumor Necrosis Factor-α Polarize Bone Marrow Stromal Cells Uniformly to a Th1 Phenotype

Ping Jin, Yuanlong Zhao, Hui Liu, Jinguo Chen, Jiaqiang Ren, Jianjian Jin, Davide Bedognetti, Shutong Liu, Ena Wang, Francesco Marincola, David Stroncek

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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.

Original languageEnglish
Article number26345
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 23 May 2016

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Mesenchymal Stromal Cells
Interferons
Interferon-gamma
Tumor Necrosis Factor-alpha
Phenotype
Tumor Microenvironment
T-Lymphocytes
Indoleamine-Pyrrole 2,3,-Dioxygenase
Immunosuppressive Agents
Transcriptome
Interleukin-4
Interleukin-10
Gene Expression
Polymerase Chain Reaction
Neoplasms

ASJC Scopus subject areas

  • General

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Interferon-γ and Tumor Necrosis Factor-α Polarize Bone Marrow Stromal Cells Uniformly to a Th1 Phenotype. / Jin, Ping; Zhao, Yuanlong; Liu, Hui; Chen, Jinguo; Ren, Jiaqiang; Jin, Jianjian; Bedognetti, Davide; Liu, Shutong; Wang, Ena; Marincola, Francesco; Stroncek, David.

In: Scientific Reports, Vol. 6, 26345, 23.05.2016.

Research output: Contribution to journalArticle

Jin, Ping ; Zhao, Yuanlong ; Liu, Hui ; Chen, Jinguo ; Ren, Jiaqiang ; Jin, Jianjian ; Bedognetti, Davide ; Liu, Shutong ; Wang, Ena ; Marincola, Francesco ; Stroncek, David. / Interferon-γ and Tumor Necrosis Factor-α Polarize Bone Marrow Stromal Cells Uniformly to a Th1 Phenotype. In: Scientific Reports. 2016 ; Vol. 6.
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