PXD054843
PXD054843 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | EZH2 loss during metabolic stress drives restoration of MHC Class I machinery in melanoma |
| Description | Unleashing the immune anti-tumor response through immune checkpoint blockade (ICB) has been successful in treating many solid-tumor malignancies, including metastatic melanoma. When successful, the ICB response can be potent; however, half of patients fail to respond. ICB responsiveness is impacted by the harsh solid tumor microenvironment (TME), which is characterized by metabolic stress. The TME impacts tumor antigenicity, with ICB-responsive melanomas exhibiting increased major histocompatibility complex class I (MHC-I) expression. Further investigation of tumor immunogenicity in the context of the TME may improve cellular therapies. Here, we define and characterize an epigenetic mechanism regulating melanoma antigen presentation driven by prolonged metabolic stress. Murine and human melanoma cell lines were cultured under prolonged metabolic stress, forcing cells to adapt to the absence of glucose. Melanoma cells adapted to the absence of glucose have IFN-gamma-independent increases in MHC-I and an increased sensitivity to T cell-mediated killing. Proteomic analysis revealed dysregulation of histone epigenetic modifiers under prolonged metabolic stress, specifically loss of histone methyltransferase EZH2 (Enhancer of Zeste Homolog 2). EZH2 directly silences gene transcription via catalyzing H3K27me3. Following metabolic adaptation, ChIP-sequencing and ChIP-PCR revealed H3K27me3 loss at genes specific to MHC-I antigen presentation. Prolonged metabolic stress in melanoma cells blunt EZH2 levels and H3K27me3 levels at promoters of genes regulating MHC-I presentation, resulting in elevated MHC-I antigenicity and increased CD8+ T cell killing. This demonstrates potential for EZH2 abundance and mutational status as a prognostic indicators of ICB-responsiveness in metastatic melanoma and supports EZH2 inhibition as adjuvant for immunotherapies |
| HostingRepository | MassIVE |
| AnnounceDate | 2025-04-07 |
| AnnouncementXML | Submission_2025-04-07_12:50:09.652.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Stephanie Byrum |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | Oxidation |
| Instrument | Orbitrap Eclipse |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-08-13 05:57:31 | ID requested | |
| ⏵ 1 | 2025-04-07 12:50:10 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: melanoma, metabolic stress, EZH2, immune checkpoint |
Contact List
| Brian Koss | |
|---|---|
| contact affiliation | University of Arkansas for Medical Sciences |
| contact email | BSKoss@uams.edu |
| lab head | |
| Stephanie Byrum | |
| contact affiliation | St Jude Children's Research Hospital |
| contact email | sbyrum@stjude.org |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive-ftp.ucsd.edu/v08/MSV000095589/ |
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