ArticleThe Journal of clinical investigation2019
Tumor suppressor TET2 promotes cancer immunity and immunotherapy efficacy.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers.
What it found
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The trial behind it
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
148 citing papers in PubMed, 224 citations in OpenAlex.
- Rewiring of de novo serine synthesis supports tumorigenesis under deficiency of TET2.British journal of cancer · 2026Article
- Loss of TET2 sulfhydration results in destabilization of TET2 and down-regulation of the immune response in melanoma.Acta pharmaceutica Sinica. B · 2026Article
- Tumor cell-intrinsic TET3 restrains type I interferon signaling and anti-tumor immunity.Science China. Life sciences · 2026Article
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Therapeutic repurposing of old drugs to modulate the tumor immune microenvironment and enhance immunotherapy efficacy.Journal of pharmaceutical analysis · 2026Review
- Genomic profiling and therapeutic targets of Thai melanoma revealed by next-generation sequencing.Scientific reports · 2026Article
- Tet2 modulates ER stress responses related to β-cell death and autoimmunity in diabetes.iScience · 2026Article
- High-dose vitamin C: A promising anti-tumor agent, insight from mechanisms, clinical research, and challenges.Genes & diseases · 2026Review
- Genetic dissection of signalling pathways that mediate iron-related tumor growth in a Drosophila model.PLoS genetics · 2026Article
- Loss of ten-eleven translocation 2 (TET2) facilitates aggressive behaviour in cutaneous melanoma by inducing peroxisome proliferator-activated receptor-γ coactivator 1α expression and oxidative phosphorylation.The British journal of dermatology · 2026Article
- Targeting CPS1 attenuates lung cancer metastasis by regulating EMT through an epigenetic mechanism.Theranostics · 2026Article
- Epigenetic and metabolic plasticity of tumor cells in immunotherapy resistance.Frontiers in immunology · 2026Review
- From intracellular drivers to immune modulators: emerging paradigms in oncogenic pathway-directed immunotherapy optimization.Cell communication and signaling : CCS · 2025Review
- FOXM1 upregulation, promotes immune escape in gastric cancer through activation of Notch signaling pathway.Molecular and cellular biochemistry · 2025Article
- Porcine GWAS identifies ACOT11 as regulator for macrophage IL-1β maturation via IFNGR2 palmitoylation.Science China. Life sciences · 2025Article
- TET2 has endothelial-specific roles in interferon responses that are dysregulated by hyperglycemia in vitro and in vivo.The Journal of biological chemistry · 2025Article
- Single-Cell Analysis Reveals that Vitamin C Inhibits Bone Metastasis of Renal Cancer via Cell Cycle Arrest and Microenvironment Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- USP15 Facilitates Colorectal Cancer Immune Evasion through SMYD3/CCL2-Dependent Myeloid-Derived Suppressor Cell Recruitment.Cancer immunology research · 2025Article
- Reprogramming tumor-associated macrophages and blocking PD-L1 via engineered outer membrane vesicles to enhance T cell infiltration and cytotoxic functions.Journal of nanobiotechnology · 2025Article
88 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Loss-of-function mutations in genes encoding TET DNA dioxygenase occur frequently in hematopoietic malignancy, but rarely in solid tumors which instead commonly have reduced activity. The impact of decreased TET activity in solid tumors is not known. Here we show that TET2 mediates interferon γ (IFNγ)-JAK-STAT signaling pathway to control chemokine and PD-L1 expression, lymphocyte infiltration and cancer immunity. IFNγ stimulated STAT1 to bind TET2 and recruit TET2 to hydroxymethylate chemokine and PD-L1 genes. Reduced TET activity was associated with decreased TH1-type chemokines and tumor-infiltrating lymphocytes (TILs) and the progression of human colon cancer. Deletion of Tet2 in murine melanoma and colon tumor cells reduced chemokine expression and TILs, enabling tumors to evade anti-tumor immunity and to resist anti-PD-L1 therapy. Conversely, stimulating TET activity by systematic injection of its co-factor, ascorbate/vitamin C, increased chemokine and TILs, leading to enhanced anti-tumor immunity and anti-PD-L1 efficacy and extended lifespan of tumor-bearing mice. These results suggest an IFNγ-JAK-STAT-TET signaling pathway that mediates tumor response to anti-PD-L1/PD-1 therapy and is frequently disrupted in solid tumors. Our findings also suggest TET activity as a biomarker for predicting the efficacy and patient response to anti-PD-1/PD-L1 therapy, and stimulating TET activity as an adjuvant immunotherapy of solid tumors.
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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.