ArticleNature cancer2021
EZH2 inhibition activates a dsRNA-STING-interferon stress axis that potentiates response to PD-1 checkpoint blockade in prostate cancer.
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Article in Nature cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 6 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed, 6 pooled it
13.5field-weighted citation impact, top 1% of its field
What it found
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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
168 citing papers in PubMed, 6 syntheses or guidelines pooled it, 232 citations in OpenAlex.
- Clinical Benefit and Safety of Combined Immunotherapy and Targeted Therapy in Prostate Cancer.International journal of cancer · 2026Pooled it
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 5: Epigenetic Regulation of PD-L1.International journal of molecular sciences · 2021Pooled it
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment.International journal of molecular sciences · 2021Pooled it
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models).International journal of molecular sciences · 2021Pooled it
- Pooled it
- Pooled it
- The therapeutic potential of transposable element activity modulation.EMBO molecular medicine · 2026Review
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- Therapy induced senescence promotes immunogenicity in acute myeloid Leukemia through reduced EZH2 activity.Nature communications · 2026Article
- Tumor cell-intrinsic TET3 restrains type I interferon signaling and anti-tumor immunity.Science China. Life sciences · 2026Article
- Breaking the immune "cold niche" in bone metastasis: core mechanisms of the multidimensional interwoven regulatory network and precision breakthrough strategies.Molecular cancer · 2026Review
- Breaking bone-associated tumor vicious cycle through macrophage membrane-camouflaged nanodecoys for sonodynamic/epigenetic therapeutics of oral squamous cell carcinoma.Journal of nanobiotechnology · 2026Article
- In vivo CRISPR screens identify CBX4 as an epigenetic regulator for cancer immunotherapy.The Journal of clinical investigation · 2026Article
- Dual function of DOT1L suppresses tumor cell-intrinsic immunogenicity in hepatocellular carcinoma.Oncogene · 2026Article
- Epigenetic orchestration of cancer-immune dynamics: mechanisms, technologies, and clinical advancements.Journal of advanced research · 2026Review
- Genomic and Immune Correlates of EZH2 Expression and Activity in Olfactory Neuroblastoma.Head & neck · 2026Article
- A dual role of EZH2 in regulating A-to-I RNA editing and mRNA stability through ADAR.Nature communications · 2026Article
- Cancer metabolism in radiation sensitization - complementary roles of O-GlcNAc transferase and PARP1.Journal of cell science · 2026Article
- EZH2 Suppression Diversifies Prostate Cancer Lineage Variant Evolution and Lacks Efficacy in Inhibiting Disease Progression.Cancer research · 2026Article
- PD-L1 Expression in Prostate Cancer: Anatomopathological Features, Methodological Pitfalls, and Therapeutic Potential.International journal of molecular sciences · 2026Review
108 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
37 authors at 13 institutions in 2 countries.
Katherine L Morel *Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7968-4032
Anjali V Sheahan *Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Deborah L BurkhartDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Sylvan C BacaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nadia BoufaiedCancer Research Program, Research Institute of the McGill University Health Centre, Montréal, Canada.
Yin LiuDepartment of Medical Biophysics, University of Toronto and Princess Margaret Cancer Center University Health Network, Toronto, Canada.
Xintao QiuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8560-7017
Israel CañadasBlood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
Kevin RoehleDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Max HecklerDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Carla CalaguaDepartment of Medicine, Hematology-Oncology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Huihui YeDepartment of Pathology, University of California at Los Angeles, Los Angeles, CA, USA.
Constantia PantelidouDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2750-9352
Phillip GalboDepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0002-5391-598X
Sukanya PanjaDepartment of Health Informatics, Rutgers School of Health Professionals, Newark, NJ, USA.
Antonina MitrofanovaDepartment of Health Informatics, Rutgers School of Health Professionals, Newark, NJ, USA.ORCID http://orcid.org/0000-0003-0671-6512
Scott WilkinsonLaboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2613-8425
Nichelle C WhitlockLaboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Shana Y TrostelLaboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Anis A HamidDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Adam S KibelDepartment of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
David A BarbieDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5422-4275
Atish D ChoudhuryDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Mark M PomerantzDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Christopher J SweeneyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Henry W LongDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6849-6629
David J EinsteinHematology and Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Geoffrey I ShapiroDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Stephanie K DouganDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Adam G SowalskyLaboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-2760-1853
Housheng Hansen HeDepartment of Medical Biophysics, University of Toronto and Princess Margaret Cancer Center University Health Network, Toronto, Canada.
Matthew L FreedmanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-0151-1238
Steven P BalkHematology and Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4546-7371
Massimo LodaDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
David P LabbéCancer Research Program, Research Institute of the McGill University Health Centre, Montréal, Canada.ORCID http://orcid.org/0000-0001-8864-8765
Brian M OlsonDepartments of Hematology and Medical Oncology and Urology, Emory University School of Medicine, Atlanta, GA, USA.
Leigh EllisDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA. Leigh.Ellis@cshs.org.ORCID http://orcid.org/0000-0003-4739-5049
Dana-Farber Cancer Institute · USNational Institutes of Health · USBeth Israel Deaconess Medical Center · USMcGill University Health Centre · CARutgers, The State University of New Jersey · USUniversity Health Network · CAAlbert Einstein College of Medicine · USBrigham and Women's Hospital · USBroad Institute · USCornell University · USEmory University · USFox Chase Cancer Center · USUniversity of California, Los Angeles · US
Funding
UCLA SPORE IN PROSTATE CANCERP50CA092131 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREEMAN, MICHAEL R · 2002 to 2023
$42.6MYAP1 and RB1 cooperate to regulate lung cancer lineage plasticity and therapeutic resistanceU24CA274159 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI DAVID W. GOODRICH, Alan David Hutson · 2022 to 2026
$8.5MMolecular alterations driving the development of primary prostate cancersZIABC011679 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SOWALSKY, ADAM · 2016 to 2025
$6.9MMechanisms of resistance to treatment in aggressive prostate cancersZIABC011838 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SOWALSKY, ADAM · 2018 to 2025
$5.7MExploiting RB1 deficiency for the treatment of lethal neuroendocrine prostate cancerR01CA207757 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI ELLIS, LEIGH, GOODRICH, DAVID W. · 2016 to 2020
$2.8MATR Dependency as a Novel Therapeutic Target in Lethal RB Deficient ProstateCancerR01CA252468 · NCI · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI Leigh Ellis · 2020 to 2026
$1.5MNRSA Training CoreTL1TR002557 · NCATS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI MARANTZ, PAUL R · 2018 to 2022
$1.0MNovel Mouse Models to define Genetic Drivers of Aggressive Prostate CancerR21CA205627 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI ELLIS, LEIGH · 2016 to 2017
$395kIntramural NIH HHS Z99 CA999999Intramural NIH HHS ZIA BC011679NCATS NIH HHS TL1 TR002557NCI NIH HHS P50 CA092131NCI NIH HHS R01 CA207757NCI NIH HHS R01 CA252468NCI NIH HHS R21 CA205627NCI NIH HHS U24 CA274159
Abstract
Prostate cancers are considered to be immunologically 'cold' tumors given the very few patients who respond to checkpoint inhibitor (CPI) therapy. Recently, enrichment of interferon-stimulated genes (ISGs) predicted a favorable response to CPI across various disease sites. The enhancer of zeste homolog-2 (EZH2) is overexpressed in prostate cancer and known to negatively regulate ISGs. In the present study, we demonstrate that EZH2 inhibition in prostate cancer models activates a double-stranded RNA-STING-ISG stress response upregulating genes involved in antigen presentation, Th1 chemokine signaling and interferon response, including programmed cell death protein 1 (PD-L1) that is dependent on STING activation. EZH2 inhibition substantially increased intratumoral trafficking of activated CD8
Indexed as
Programmed Cell Death 1 ReceptorProstatic NeoplasmsCD8-Positive T-LymphocytesEnhancer of Zeste Homolog 2 ProteinHumansInterferonsMaleRNA, Double-StrandedEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanInterferonsProgrammed Cell Death 1 ReceptorRNA, Double-Stranded
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