PXD035347 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | ULK1 as a novel therapeutic target to enhance immune checkpoint therapies against melanoma |
Description | Immune checkpoint inhibitors (ICIs) have transformed the treatment of melanoma. However, the majority of patients have primary or acquired resistance to ICIs, limiting durable responses and patient survival. Interferon-gamma (IFNg) signaling and the expression of IFNg-stimulated genes correlate with either response or resistance to ICIs, in a context-dependent manner. While IFNg-inducible immunostimulatory genes are required for response to ICIs, chronic IFNg signaling induces the expression of immunosuppressive genes, promoting resistance to these therapies. Here, we show that high levels of ULK1 correlate with poor survival in melanoma patients and overexpression of ULK1 in melanoma cells enhances IFNg-induced expression of immunosuppressive genes, with minimal effects on the expression of immunostimulatory genes. In contrast, genetic or pharmacological inhibition of ULK1 reduces expression of IFNg-induced immunosuppressive genes. ULK1 binds IRF1 in the nuclear compartment of melanoma cells, controlling its binding to the PD-L1 promoter region. Additionally, pharmacological inhibition of ULK1 in combination with anti-PD-1 therapy further reduces melanoma tumor growth and enhances anti-tumor immune responses in vivo. Our data suggest that targeting ULK1 represses IFNg-dependent immunosuppression. These findings support the combination of ULK1 drug-targeted inhibition with ICIs for the treatment of melanoma patients to improve response rates and patient outcomes. |
HostingRepository | PRIDE |
AnnounceDate | 2023-04-12 |
AnnouncementXML | Submission_2023-04-12_06:24:14.184.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | RenuGoel |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-07-14 07:25:13 | ID requested | |
1 | 2023-02-02 15:27:57 | announced | |
2 | 2023-04-11 08:30:30 | announced | 2023-04-11: Updated project metadata. |
3 | 2023-04-11 08:33:26 | announced | 2023-04-11: Updated project metadata. |
⏵ 4 | 2023-04-12 06:24:15 | announced | 2023-04-12: Updated project metadata. |
5 | 2023-11-14 07:33:39 | announced | 2023-11-14: Updated project metadata. |
Publication List
Fenton SE, Zannikou M, Ilut L, Fischietti M, Ji C, Oku CV, Horvath CM, Le Poole IC, Bosenberg M, Bartom ET, Kocherginsky M, Platanias LC, Saleiro D, -Mediated Resistance to Immune Checkpoint Inhibitors. Mol Cancer Res, 21(4):332-344(2023) [pubmed] |
Keyword List
submitter keyword: IRF1, interferon-gamma,ULK1, melanoma, PD-L1, signaling, immune checkpoint inhibitors |
Contact List
Leonidas C.Platanias |
contact affiliation | Director, Robert H. Lurie Comprehensive Cancer Center Jesse, Sara, Andrew, Abigail, Benjamin and Elizabeth Lurie Professor of Oncology Professor of Medicine (Hematology and Oncology) and Biochemistry and Molecular Genetics |
contact email | I-platanias@northwestern.edu |
lab head | |
RenuGoel |
contact affiliation | Northwestern University |
contact email | drrenugoel@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD035347
- Label: PRIDE project
- Name: ULK1 as a novel therapeutic target to enhance immune checkpoint therapies against melanoma