ArticleScience advances2015
The PTEN pathway in Tregs is a critical driver of the suppressive tumor microenvironment.
Article in Science advances, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.
- COVID-19-Associated acute respiratory distress syndrome (CARDS): Mechanistic insights on therapeutic intervention and emerging trends.International immunopharmacology · 2021Pooled it
- Improving Immune Checkpoint Therapy in the Tumor Microenvironment by Targeting T Cell Metabolism.Endocrine, metabolic & immune disorders drug targets · 2026Review
- Regulatory T cells in the tumour microenvironment.Nature reviews. Cancer · 2025Review
- Metabolic checkpoints in immune cell reprogramming: rewiring immunometabolism for cancer therapy.Molecular cancer · 2025Review
- Immunometabolism of regulatory T cells in cancer.Oncogene · 2025Review
- Lymph node macrophages drive immune tolerance and resistance to cancer therapy by induction of the immune-regulatory cytokine IL-33.Cancer cell · 2025Article
- Vps34-orchestrated lipid signaling processes regulate the transitional heterogeneity and functional adaptation of effector regulatory T cells.PLoS biology · 2025Article
- Tumor suppressor genes in the tumor microenvironment.Disease models & mechanisms · 2025Review
- Anti-PD-1 amplifies costimulation in melanoma-infiltrating TJournal for immunotherapy of cancer · 2025Article
- CDK1 Acts as a Prognostic Biomarker Associated with Immune Infiltration in Pan-cancer, Especially in Gastrointestinal Tumors.Current medicinal chemistry · 2025Article
- Infiltrating treg reprogramming in the tumor immune microenvironment and its optimization for immunotherapy.Biomarker research · 2024Review
- Complex Role of Regulatory T Cells (Tregs) in the Tumor Microenvironment: Their Molecular Mechanisms and Bidirectional Effects on Cancer Progression.International journal of molecular sciences · 2024Review
- Targeting CXCR4 impaired T regulatory function through PTEN in renal cancer patients.British journal of cancer · 2024Article
- Review
- Lipid metabolism in tumor-infiltrating regulatory T cells: perspective to precision immunotherapy.Biomarker research · 2024Review
- Tumor-infiltrating mast cells stimulate ICOSJournal of advanced research · 2024Article
- Phosphorylation of hnRNP A1-Serine 199 Is Not Required for T Cell Differentiation and Function.ImmunoHorizons · 2024Article
- Research progress on the role of PTEN deletion or mutation in the immune microenvironment of glioblastoma.Frontiers in oncology · 2024Review
- Reprogramming of regulatory T cells in inflammatory tumor microenvironment: can it become immunotherapy turning point?Frontiers in immunology · 2024Review
- Modulating Treg stability to improve cancer immunotherapy.Trends in cancer · 2023Review
56 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
The tumor microenvironment is profoundly immunosuppressive. We show that multiple tumor types create intratumoral immune suppression driven by a specialized form of regulatory T cell (Treg) activation dependent on the PTEN (phosphatase and tensin homolog) lipid phosphatase. PTEN acted to stabilize Tregs in tumors, preventing them from reprogramming into inflammatory effector cells. In mice with a Treg-specific deletion of PTEN, tumors grew slowly, were inflamed, and could not create an immunosuppressive tumor microenvironment. In normal mice, exposure to apoptotic tumor cells rapidly elicited PTEN-expressing Tregs, and PTEN-deficient mice were unable to maintain tolerance to apoptotic cells. In wild-type mice with large established tumors, pharmacologic inhibition of PTEN after chemotherapy or immunotherapy profoundly reconfigured the tumor microenvironment, changing it from a suppressive to an inflammatory milieu, and tumors underwent rapid regression. Thus, the immunosuppressive milieu in tumors must be actively maintained, and tumors become susceptible to immune attack if the PTEN pathway in Tregs is disrupted.
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