Comparative transcriptome analysis reveals distinct genetic modules associated with Helios expression in intratumoral regulatory T cells
Open accessAbstract
Significance: Regulatory T cells (Tregs) play a critical role in inflammatory, autoimmune, and antitumor immune responses. Increased expression of transcription factor Helios by tumor-infiltrating Tregs can enhance immune-suppressive activity, while deletion of Helios promotes an effector T helper (Th) cell phenotype that can contribute to the host antitumor immune response. We report that chronic inflammatory conditions of tumors induce Helios-deficient Tregs to express increased levels of genes associated with T cell activation and Th cell differentiation. Helios-dependent changes in gene expression are restricted to tumor sites and not observed in peripheral lymphoid tissues. We suggest that Helios-deficient Tregs that recognize tumor-associated self-antigens may become unstable in the tumor microenvironment and undergo reprogramming into effector T cells that can inhibit tumor growth.
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Helios is critical for maintaining the identity, anergic phenotype, and suppressive activity of regulatory T cells.
“The zinc finger transcription factor Helios is critical for maintaining the identity, anergic phenotype, and suppressive activity of regulatory T cells.”
From Acute pharmacological degradation of Helios destabilizes regulatory T cells (2021) · cites this paper as [7]
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References 29 · Cited by 55
- Authors
- Yates, K., Bi, K., Haining, W. N., Cantor, H., & Kim, H.-J.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Broad Institute (US)
- Harvard University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2018-02-09
- Volume
- 115
- Issue
- 9
- Pages
- 2162-2167
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5834721
- OpenAlex
- W2792220974
- Cited by
- 55
- References
- 29
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 8 · 2023: 5 · 2022: 4 · 2021: 11 · 2020: 6 · 2019: 8 · 2018: 1
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Office of Extramural Research, National Institutes of Health (R01AI037562)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- Helios, regulatory T cells, tumor microenvironment, T helper cell differentiation, GITR, PD-1, T cell receptor signaling, costimulatory receptors, tumor immunology, immune tolerance
- MeSH terms
- Animals, Bacterial Proteins, DNA-Binding Proteins, Luminescent Proteins, Melanoma, Mice, Inbred C57BL, Neoplasms, Experimental, Transcription Factors, Gene Expression Regulation, Neoplastic, Mice, Knockout, Gene Expression Profiling, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors
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