ArticleThe Journal of clinical investigation2020
Inhibiting the coregulator CoREST impairs Foxp3+ Treg function and promotes antitumor immunity.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 69 citations in OpenAlex.
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- Intratumoral regulatory T cells are associated with treatment response to neoadjuvant chemotherapy and prognosis in gastroesophageal adenocarcinoma.Oncoimmunology · 2025Article
- Hypoxia-induced RCOR2 promotes macrophage M2 polarization and CD8Journal for immunotherapy of cancer · 2025Article
- CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond.Science advances · 2025Review
- The epigenetic hallmarks of immune cells in cancer.Molecular cancer · 2025Review
- REST corepressor 2 contributes to the cell proliferation of endometrial cancer.Frontiers in oncology · 2025Article
- Hyperactivating EZH2 to augment H3K27me3 levels in regulatory T cells enhances immune suppression by driving early effector differentiation.Cell reports · 2024Article
- Effects of conceptus proteins on endometrium and blood leukocytes of dairy cattle using transcriptome and meta-analysis.bioRxiv : the preprint server for biology · 2024Article
- The CoREST repressor complex mediates phenotype switching and therapy resistance in melanoma.The Journal of clinical investigation · 2024Article
- RCOR1 is targeted by miR-23b-3p to modulate growth, colony formation, migration, and invasion of prostate cancer cells.International journal of clinical and experimental pathology · 2024Article
- Advances in Foxp3+ regulatory T cells (Foxp3+ Treg) and key factors in digestive malignancies.Frontiers in immunology · 2024Review
- Epigenetic regulation of human FOXP3+ Tregs: from homeostasis maintenance to pathogen defense.Frontiers in immunology · 2024Review
- Genetic Association and Differential RNA Expression of Histone (De)Acetylation-Related Genes in Pemphigus Foliaceus-A Possible Epigenetic Effect in the Autoimmune Response.Life (Basel, Switzerland) · 2023Article
- Evolution of lysine-specific demethylase 1 and REST corepressor gene families and their molecular interaction.Communications biology · 2023Article
- Modulating Treg stability to improve cancer immunotherapy.Trends in cancer · 2023Review
- LSD1: an emerging face in altering the tumor microenvironment and enhancing immune checkpoint therapy.Journal of biomedical science · 2023Review
- Targeting intracellular proteins with cell type-specific functions for cancer immunotherapy.Life medicine · 2023Review
- Identification of the Prognostic Biomarkers CBX6 and CBX7 in Bladder Cancer.Diagnostics (Basel, Switzerland) · 2023Article
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Foxp3+ Tregs are key to immune homeostasis, but the contributions of various large, multiprotein complexes that regulate gene expression remain unexplored. We analyzed the role in Tregs of the evolutionarily conserved CoREST complex, consisting of a scaffolding protein, Rcor1 or Rcor2, plus Hdac1 or Hdac2 and Lsd1 enzymes. Rcor1, Rcor2, and Lsd1 were physically associated with Foxp3, and mice with conditional deletion of Rcor1 in Foxp3+ Tregs had decreased proportions of Tregs in peripheral lymphoid tissues and increased Treg expression of IL-2 and IFN-γ compared with what was found in WT cells. Mice with conditional deletion of the gene encoding Rcor1 in their Tregs had reduced suppression of homeostatic proliferation, inability to maintain long-term allograft survival despite costimulation blockade, and enhanced antitumor immunity in syngeneic models. Comparable findings were seen in WT mice treated with CoREST complex bivalent inhibitors, which also altered the phenotype of human Tregs and impaired their suppressive function. Our data point to the potential for therapeutic modulation of Treg functions by pharmacologic targeting of enzymatic components of the CoREST complex and contribute to an understanding of the biochemical and molecular mechanisms by which Foxp3 represses large gene sets and maintains the unique properties of this key immune cell.
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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.