ArticleiScience2018
YY1 Upregulates Checkpoint Receptors and Downregulates Type I Cytokines in Exhausted, Chronically Stimulated Human T Cells.
Article in iScience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 91 citations in OpenAlex.
- Article
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- Modifying Epigenetic Landscapes to Restore Immune Therapeutic Responses in Triple Negative Breast Cancer.Cancers · 2026Review
- A post-translational regulatory map of chronic antigen-driven human T cell dysfunction.bioRxiv : the preprint server for biology · 2026Article
- HDAC1 modulates sepsis-induced immunosuppression by driving the exhaustion of CD8+ T cells.JCI insight · 2026Article
- Upregulation of TNFR2 Precedes TOX Expression by Exhausted T cells and Restricts Antitumor and Antiviral Immunity.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Molecular pixelation of the CAR T cell surface proteome.bioRxiv : the preprint server for biology · 2026Article
- Distinct control of T cell proliferation and effector function by partitioning of intracellular sulfur from cysteine.bioRxiv : the preprint server for biology · 2026Article
- Reversing T cell dysfunction in a novelFrontiers in immunology · 2026Article
- The YYR (YY1- RKIP) Regulatory Axis in the pathogenesis of Cancer and Immune Evasion.Journal of experimental & clinical cancer research : CR · 2025Review
- Clinical Significance of Nuclear Yin-Yang Overexpression Evaluated by Immunohistochemistry in Tissue Microarrays and Digital Pathology Analysis: A Useful Prognostic Tool for Breast Cancer.International journal of molecular sciences · 2025Article
- Targeting EZH2 in autoimmune diseases: unraveling epigenetic regulation and therapeutic potential.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Upregulation of YY1/EZH2 and MLH1 as Therapeutic Targets for Adult T-Cell Leukemia/Lymphoma.Cancer science · 2025Article
- Enhancer zeste homolog 2 (EZH2) targeting by small interfering RNA (siRNA); recent advances and prospect.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Characterization of the aryl hydrocarbon receptor as a potential candidate to improve cancer T cell therapies.Cancer immunology, immunotherapy : CII · 2025Article
- Polycomb repressive complex 2 (PRC2) pathway's role in cancer cell plasticity and drug resistance.Functional & integrative genomics · 2025Review
- A B7-H3-Targeted CD28 Bispecific Antibody Enhances the Activity of Anti-PD-1 and CD3 T-cell Engager Immunotherapies.Molecular cancer therapeutics · 2025Article
- ETV7 limits the antiviral and antitumor efficacy of CD8Nature cancer · 2025Article
- Wip1 inhibitor CCT007093 alleviates immune exhaustion of lymphocytes via p65 NF-κB and YY1 in chronic hepatitis B virus infection in mice.Frontiers in immunology · 2025Article
- GSTP1 improves CAR-T cell proliferation and cytotoxicity to combat lymphoma.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cells infiltrate affected organs in chronic infections and malignancy, but they may fail to eradicate virus-infected cells or tumor because of exhaustion. This report describes a Yin Yang-1 (YY1)-centered mechanism for diverse components that have been correlated with exhaustion. Utilizing an in vitro reconstruction of chronic T cell activation, YY1 is shown to positively regulate the checkpoint receptors PD1, Lag3, and Tim3 and to negatively regulate the type I cytokines interleukin-2 (IL-2) (in collaboration with Ezh2 histone methyltransferase) and interferon gamma (IFN-?). Other tests suggest that IL-2 failure drives a large component of cytotoxic functional decline rather than solely checkpoint receptor-ligand interactions that have been the focus of current anti-exhaustion therapies. Clinical evaluations confirm elevated YY1 and Ezh2 in melanoma tumor-infiltrating lymphocytes and in PD1+ T cells in patients with HIV. Exhaustion is revealed to be an active process as the culmination of repetitive two-signal stimulation in a feedback loop via CD3/CD28?p38MAPK/JNK?YY1? exhaustion.
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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.