Stat3 and Gfi-1 transcription factors control Th17 cell immunosuppressive activity via the regulation of ectonucleotidase expression
Open accessAbstract
Although Th17 cells are known to promote tissue inflammation and autoimmunity, their role during cancer progression remains elusive. Here, we showed that in vitro Th17 cells generated with the cytokines IL-6 and TGF-β expressed CD39 and CD73 ectonucleotidases, leading to adenosine release and the subsequent suppression of CD4(+) and CD8(+) T cell effector functions. The IL-6-mediated activation of the transcription factor Stat3 and the TGF-β-driven downregulation of Gfi-1 transcription factor were both essential for the expression of ectonucleotidases during Th17 cell differentiation. Stat3 supported whereas Gfi-1 repressed CD39 and CD73 expression by binding to their promoters. Accordingly, Th17 cells differentiated with IL-1β, IL-6, and IL-23 but without TGF-β did not express ectonucleotidases and were not immunosuppressive. Finally, adoptive transfer of Th17 cells induced by TGF-β and IL-6 promoted tumor growth in a CD39-dependent manner. Thus, ectonucleotidase expression supports the immunosuppressive fate of Th17 cells in cancer.
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CD39-positive Th17 cells promote tumor growth, suggesting an immunosuppressive role in cancer.
“CD39-pos Th17 cells promotes tumor growth, suggesting their immunosuppressive role in cancer”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Chalmin et al., 2012
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P2X7 Integrates PI3K/AKT and AMPK-PRAS40-mTOR Signaling Pathways to Mediate Tumor Cell Death
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Induction and stability of human Th17 cells require endogenous NOS2 and cGMP-dependent NO signaling
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Production of Adenosine by Ectonucleotidases: A Key Factor in Tumor Immunoescape
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Controlling the Immune Suppressor: Transcription Factors and MicroRNAs Regulating CD73/NT5E
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CD73-Generated Adenosine: Orchestrating the Tumor-Stroma Interplay to Promote Cancer Growth
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MYC as a Multifaceted Regulator of Tumor Microenvironment Leading to Metastasis
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Synthetic RORγ agonists regulate multiple pathways to enhance antitumor immunity
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Purinergic Signaling in the Hallmarks of Cancer
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Bilirubin suppresses Th17 immunity in colitis by upregulating CD39
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- Authors
- Chalmin, F., Mignot, G., Bruchard, M., Chevriaux, A., Végran, F., Hichami, A., Ladoire, S., Derangère, V., Vincent, J., Masson, D., Robson, S. C., Eberl, G., Pallandre, J. R., Borg, C., Ryffel, B., Apetoh, L., Rébé, C., & Ghiringhelli, F.
- Affiliations
- Inserm (FR)
- Beth Israel Deaconess Medical Center (US)
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 36
- Issue
- 3
- Pages
- 362-373
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2043291701
- Cited by
- 338
- References
- 43
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 15 · 2023: 21 · 2022: 19 · 2021: 33 · 2020: 37 · 2019: 22 · 2018: 26 · 2017: 31 · 2016: 19 · 2015: 28 · 2014: 29 · 2013: 28 · 2012: 12
- FWCI
- 21.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-10-PDOC-0014)
- National Cancer Institute (R21CA164970)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- Th17 cells, STAT3, GFI1, CD39, CD73, ectonucleotidases, adenosine, immunosuppression, tumor immunology, TGF-beta, interleukin-6, transcriptional regulation, tumor growth, adoptive transfer
- MeSH terms
- Animals, Apyrase, Binding Sites, DNA-Binding Proteins, Gene Expression Regulation, Mice, Inbred C57BL, Mice, Transgenic, Promoter Regions, Genetic, T-Lymphocytes, Transcription Factors, Antigens, CD, 5'-Nucleotidase, Interleukin-6, Transforming Growth Factor beta, Lymphocytes, Tumor-Infiltrating, Mice, Knockout, RNA, Small Interfering, STAT3 Transcription Factor, Mice, Th17 Cells
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