ArticleNature2016
Graded Foxo1 activity in Treg cells differentiates tumour immunity from spontaneous autoimmunity.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
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The trial behind it
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Who cites it
123 citing papers in PubMed, 187 citations in OpenAlex.
- Augmentation of IFN-γ+ CD8+ T cell responses correlates with survival of HCC patients on sorafenib therapy.JCI insight · 2019Trial
- Computational identification and experimental validation of shared diagnostic biomarkers and gene signatures across HLA-B27-associated immune-mediated diseases.Journal of translational medicine · 2026Article
- Phase I Trial of Ipatasertib plus Atezolizumab Enhances PI3K/AKT Pathway Immune Responses in Solid Tumors and Refractory Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Endocardial TIE2 orchestrates cardiac trabeculation via sequestering FOXO1 within the cytoplasm and stimulating versican cleavage.Development (Cambridge, England) · 2026Article
- Targeting DGAT1 reprograms lipid landscape and restores CD8⁺ T cell immunity in pancreatic cancer.Nature communications · 2026Article
- Role of immune cells in clear cell ovarian cancer: a two-sample bidirectional Mendelian randomization study.Journal of ovarian research · 2026Article
- Uncovering the dynamics of extracellular vesicle microRNA trafficking in multiple sclerosis: delivery, diversion and retention.Extracellular vesicles and circulating nucleic acids · 2026Review
- Regulatory T cells in bullous pemphigoid: biological characteristics, dysfunction, and pathogenic roles.Frontiers in immunology · 2026Review
- Intratumoral regulatory T cells are associated with treatment response to neoadjuvant chemotherapy and prognosis in gastroesophageal adenocarcinoma.Oncoimmunology · 2025Article
- Immunometabolism of regulatory T cells in cancer.Oncogene · 2025Review
- FAM207A acts as a novel and potential biomarker in lung adenocarcinoma and shapes the immunesuppressive tumor microenvironment.Clinical and experimental medicine · 2025Article
- Vps34-orchestrated lipid signaling processes regulate the transitional heterogeneity and functional adaptation of effector regulatory T cells.PLoS biology · 2025Article
- Tumor-derived colorectal cancer organoids induce a unique Treg cell population by directing CD4iScience · 2025Article
- Regulatory T Cell Metabolism: A Promising Therapeutic Target for Cancer Treatment?Immune network · 2025Review
- Early Growth Response Gene 1 Benefits Autoimmune Disease by Promoting Regulatory T Cell Differentiation as a Regulator of Foxp3.Research (Washington, D.C.) · 2025Article
- Targeting the PI3K/AKT/mTOR pathway in lung cancer: mechanisms and therapeutic targeting.Frontiers in pharmacology · 2025Review
- Prediction of prognosis, efficacy of lung adenocarcinoma by machine learning model based on immune and metabolic related genes.Discover oncology · 2024Article
- Activated PI3Kδ Specifically Perturbs Mouse Regulatory T Cell Homeostasis and Function Leading to Immune Dysregulation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases.Nature reviews. Immunology · 2024Review
- RIPK1 plays a crucial role in maintaining regulatory T-Cell homeostasis by inhibiting both RIPK3- and FADD-mediated cell death.Cellular & molecular immunology · 2024Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Regulatory T (Treg) cells expressing the transcription factor Foxp3 have a pivotal role in maintaining immunological self-tolerance; yet, excessive Treg cell activities suppress anti-tumour immune responses. Compared to the resting Treg (rTreg) cell phenotype in secondary lymphoid organs, Treg cells in non-lymphoid tissues exhibit an activated Treg (aTreg) cell phenotype. However, the function of aTreg cells and whether their generation can be manipulated are largely unexplored. Here we show that the transcription factor Foxo1, previously demonstrated to promote Treg cell suppression of lymphoproliferative diseases, has an unexpected function in inhibiting aTreg-cell-mediated immune tolerance in mice. We find that aTreg cells turned over at a slower rate than rTreg cells, but were not locally maintained in tissues. aTreg cell differentiation was associated with repression of Foxo1-dependent gene transcription, concomitant with reduced Foxo1 expression, cytoplasmic localization and enhanced phosphorylation at the Akt sites. Treg-cell-specific expression of an Akt-insensitive Foxo1 mutant prevented downregulation of lymphoid organ homing molecules, and impeded Treg cell homing to non-lymphoid organs, causing CD8(+) T-cell-mediated autoimmune diseases. Compared to Treg cells from healthy tissues, tumour-infiltrating Treg cells downregulated Foxo1 target genes more substantially. Expression of the Foxo1 mutant at a lower dose was sufficient to deplete tumour-associated Treg cells, activate effector CD8(+) T cells, and inhibit tumour growth without inflicting autoimmunity. Thus, Foxo1 inactivation is essential for the migration of aTreg cells that have a crucial function in suppressing CD8(+) T-cell responses; and the Foxo signalling pathway in Treg cells can be titrated to break tumour immune tolerance preferentially.
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Registered trials
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.