ArticleThe Journal of clinical investigation2022
Reversal of viral and epigenetic HLA class I repression in Merkel cell carcinoma.
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Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27citing papers in PubMed
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Who cites it
27 citing papers in PubMed, 29 citations in OpenAlex.
- Reprogramming engineered autologous T cells to overcome resistance in patients with Merkel cell carcinoma.Science translational medicine · 2026Trial
- ATR inhibition induces NF-κB-dependent immunogenicity in Merkel cell carcinoma independent of cGAS-STING.NPJ precision oncology · 2026Article
- Long-term major histocompatibility complex class I suppression in astronauts and clinical implications.Communications biology · 2026Review
- Viral persistence and host-state remodeling in virus-associated cancers.Archives of microbiology · 2026Review
- Targeted degradation of MDM2 overcomes feedback regulation of p53 signaling in Merkel cell carcinoma models.The Journal of clinical investigation · 2026Article
- Efficacy of Immune Checkpoint Inhibitors and Oncoviruses in Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Article
- EZH2-TTP-mTORC1 Axis Drives Phenotypic Plasticity and Therapeutic Vulnerability in Lethal Prostate Cancer.bioRxiv : the preprint server for biology · 2025Article
- IMPDH inhibition induces DNA replication stress and ATR sensitivity in Merkel cell carcinoma.iScience · 2025Article
- Systematic identification of minor histocompatibility antigens predicts outcomes of allogeneic hematopoietic cell transplantation.Nature biotechnology · 2025Article
- HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy.Cell · 2025Article
- Understanding Merkel Cell Carcinoma: Pathogenic Signaling, Extracellular Matrix Dynamics, and Novel Treatment Approaches.Cancers · 2025Review
- Article
- Cancer cell-intrinsic biosynthesis of itaconate promotes tumor immunogenicity.The EMBO journal · 2024Article
- Intratumoral STING agonist reverses immune evasion in PD-(L)1-refractory Merkel cell carcinoma: mechanistic insights from detailed biomarker analyses.Journal for immunotherapy of cancer · 2024Article
- Review
- Merkel cell polyomavirus small tumor antigen contributes to immune evasion by interfering with type I interferon signaling.PLoS pathogens · 2024Article
- Merkel Cell Carcinoma: Integrating Epidemiology, Immunology, and Therapeutic Updates.American journal of clinical dermatology · 2024Review
- T antigen-specific CD8+ T cells associate with PD-1 blockade response in virus-positive Merkel cell carcinoma.The Journal of clinical investigation · 2024Article
- Immune-check blocking combination multiple cytokines shown curative potential in mice tumor model.Cancer medicine · 2023Article
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Authors and funding
46 authors at 9 institutions in 3 countries.
Patrick C LeeDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Susan KlaegerBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Phuong M LeDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Keegan KorthauerDepartment of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
Jingwei ChengDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Varsha AnanthapadmanabhanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Thomas C FrostDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Jonathan D StevensDepartment of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Alan Yl WongDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
J Bryan IorgulescuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Anna Y TarrenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Vipheaviny A CheaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Isabel P CarulliDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Camilla K LemvighSection for Bioinformatics, Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.
Christina B PedersenSection for Bioinformatics, Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.
Ashley K GartinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Siranush SarkizovaBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Kyle T WrightDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Letitia W LiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Jason NomburgDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Shuqiang LiBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Teddy HuangTranslational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Xiaoxi LiuDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Lucas PomeranceDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Laura M DohertyDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Annie M ApffelBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Luke J WallaceBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Suzanna RachimiBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Kristen D FeltCenter for Immuno-Oncology and.
Jacquelyn O WolffCenter for Immuno-Oncology and.
Elizabeth WittenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Wandi ZhangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Donna NeubergDepartment of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
William J LaneHarvard Medical School, Boston, Massachusetts, USA.
Guanglan ZhangDepartment of Computer Science, Metropolitan College, Boston University, Boston, Massachusetts, USA.
Lars R OlsenSection for Bioinformatics, Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.
Manisha ThakuriaHarvard Medical School, Boston, Massachusetts, USA.
Scott J RodigDepartment of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Karl R ClauserBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Gabriel J StarrettLaboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
John G DoenchBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Sara J BuhrlageDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Steven A CarrBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
James A DeCaprioDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Catherine J WuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Derin B KeskinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Broad Institute · USDana-Farber Cancer Institute · USBrigham and Women's Hospital · USHarvard University · USCopenhagen University Hospital · DKBoston University · USNational Cancer Institute · USTechnical University of Denmark · DKUniversity of British Columbia · CA
Funding
VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI Irene M. Ghobrial · 1985 to 2026
$330.6MTreating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI David McDermott · 2003 to 2026
$53.4MMedical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0MCancer Immune Monitoring and Analysis CenterU24CA224331 · NCI · DANA-FARBER CANCER INST · PI FRANK S HODI, Catherine Ju-Ying Wu · 2017 to 2026
$18.4MTraining Program in Nervous System TumorsK12CA090354 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI PLOTKIN, SCOTT R · 2001 to 2025
$16.3MTraining Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8MMedical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7MPersonal tumor neoantigens for immunity against chronic lymphocytic leukemiaR01CA155010 · NCI · DANA-FARBER CANCER INST · PI Catherine Ju-Ying Wu · 2011 to 2026
$9.6MPROJECT 4: Interrogating PP2A Signaling in Human CancersP01CA203655 · NCI · DANA-FARBER CANCER INST · PI DECAPRIO, JAMES A. · 2017 to 2021
$8.0MThe DREAM B-Myb-MuvB complex controls sensitivity to DNA replication activators and inhibitorsR35CA232128 · NCI · DANA-FARBER CANCER INST · PI DECAPRIO, JAMES A. · 2019 to 2025
$7.2MMICROSCALED PROTEOGENOMICS FOR CANCER CLINICAL TRIALSU01CA214125 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ANURAG, MEENAKSHI, CARR, STEVEN A · 2017 to 2021
$7.0MCenter of Excellence for High Throughput Proteogenomic CharacterizationU24CA210986 · NCI · BROAD INSTITUTE, INC. · PI CARR, STEVEN A, GILLETTE, MICHAEL A · 2016 to 2020
$6.4MNCI NIH HHS K12 CA090354NCI NIH HHS P01 CA203655NCI NIH HHS P30 CA006516NCI NIH HHS P50 CA101942NCI NIH HHS R01 CA155010NCI NIH HHS R01 CA173023NCI NIH HHS R21 CA216772NCI NIH HHS R35 CA232128NCI NIH HHS R50 CA243777NCI NIH HHS R50 CA251956NCI NIH HHS U01 CA214125NCI NIH HHS U24 CA210986NCI NIH HHS U24 CA224331NCI NIH HHS U24 CA270823NHGRI NIH HHS T32 HG002295NHLBI NIH HHS R01 HL131768NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM144273
Abstract
Cancers avoid immune surveillance through an array of mechanisms, including perturbation of HLA class I antigen presentation. Merkel cell carcinoma (MCC) is an aggressive, HLA-I-low, neuroendocrine carcinoma of the skin often caused by the Merkel cell polyomavirus (MCPyV). Through the characterization of 11 newly generated MCC patient-derived cell lines, we identified transcriptional suppression of several class I antigen presentation genes. To systematically identify regulators of HLA-I loss in MCC, we performed parallel, genome-scale, gain- and loss-of-function screens in a patient-derived MCPyV-positive cell line and identified MYCL and the non-canonical Polycomb repressive complex 1.1 (PRC1.1) as HLA-I repressors. We observed physical interaction of MYCL with the MCPyV small T viral antigen, supporting a mechanism of virally mediated HLA-I suppression. We further identify the PRC1.1 component USP7 as a pharmacologic target to restore HLA-I expression in MCC.
Indexed as
Carcinoma, Merkel CellMerkel cell polyomavirusPolyomavirus InfectionsSkin NeoplasmsAntigens, Viral, TumorEpigenesis, GeneticHumansUbiquitin-Specific Peptidase 7Antigens, Viral, TumorUbiquitin-Specific Peptidase 7USP7 protein, humanMHC class 1OncologyProteomicsSkin cancer
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