ArticleProceedings of the National Academy of Sciences of the United States of America2016
Instability of Helios-deficient Tregs is associated with conversion to a T-effector phenotype and enhanced antitumor immunity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 163 citations in OpenAlex.
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- The Multifaceted Role of Regulatory T Cells in Sepsis: Mechanisms, Heterogeneity, and Pathogen-Tailored Therapies.International journal of molecular sciences · 2025Review
- The Streptomyces Metabolite Thiostrepton Inhibits Regulatory T Cell Differentiation and Function to Boost Antitumor Immune Responses.European journal of immunology · 2025Article
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- The response to anti-PD-1 and anti-LAG-3 checkpoint blockade is associated with regulatory T cell reprogramming.Science translational medicine · 2025Article
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- Anti-PD-1 amplifies costimulation in melanoma-infiltrating TJournal for immunotherapy of cancer · 2025Article
- Generation of Human Chimeric Antigen Receptor Regulatory T Cells.Journal of visualized experiments : JoVE · 2025Article
- Regulatory T cell transdifferentiation as a driver of obesity and diabetes.Frontiers in immunology · 2025Review
51 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Expression of the transcription factor Helios by Tregs ensures stable expression of a suppressive and anergic phenotype in the face of intense inflammatory responses, whereas Helios-deficient Tregs display diminished lineage stability, reduced FoxP3 expression, and production of proinflammatory cytokines. Here we report that selective Helios deficiency within CD4 Tregs leads to enhanced antitumor immunity through induction of an unstable phenotype and conversion of intratumoral Tregs into T effector cells within the tumor microenvironment. Induction of an unstable Treg phenotype is associated with enhanced production of proinflammatory cytokines by tumor-infiltrating but not systemic Tregs and significantly delayed tumor growth. Ab-dependent engagement of Treg surface receptors that result in Helios down-regulation also promotes conversion of intratumoral but not systemic Tregs into T effector cells and leads to enhanced antitumor immunity. These findings suggest that selective instability and conversion of intratumoral CD4 Tregs through genetic or Ab-based targeting of Helios may represent an effective approach to immunotherapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.