PXD029884-1

PXD029884 is an original dataset announced via ProteomeXchange.

Title	MEK inhibition enhances presentation of targetable MHC-I tumor antigens in mutant melanomas - targeted data
Description	Combining multiple therapeutic strategies in NRAS/BRAF mutant melanoma – namely MEK/BRAF kinase inhibitors, immune checkpoint inhibitors, and targeted immunotherapies – may offer an improved survival benefit by overcoming limitations associated with any individual therapy. Still, optimal combination, order, and timing of administration remains under investigation. Here, we measure how MEK inhibition alters anti-tumor immunity by utilizing quantitative immunopeptidomics to profile changes the peptide MHC (pMHC) repertoire. These data reveal a collection of tumor antigens whose presentation levels are selectively augmented following therapy, including several epitopes present at over 1000 copies-per-cell. We leveraged the tunable abundance of MEKi-modulated antigens by targeting 4 epitopes with pMHC-specific T cell engagers and antibody drug conjugates, enhancing cell killing in tumor cells following MEK inhibition. These results highlight drug treatment as a means to enhance immunotherapy efficacy by targeting specific upregulated pMHCs and provide a methodological framework for identifying, quantifying, and therapeutically targeting additional epitopes of interest.
HostingRepository	PRIDE
AnnounceDate	2023-03-11
AnnouncementXML	Submission_2023-03-10_21:08:24.435.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	LaurenStopfer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-23 07:46:03	ID requested
⏵ 1	2023-03-10 21:08:25	announced
2	2023-11-14 08:37:17	announced	2023-11-14: Updated project metadata.
3	2024-10-22 05:43:03	announced	2024-10-22: Updated project metadata.

Stopfer LE, Rettko NJ, Leddy O, Mesfin JM, Brown E, Winski S, Bryson B, Wells JA, White FM, MEK inhibition enhances presentation of targetable MHC-I tumor antigens in mutant melanomas. Proc Natl Acad Sci U S A, 119(49):e2208900119(2022) [pubmed]

submitter keyword: HLA, targeted,MHC, immunopeptidomics, antigen presentation, SureQuant

ForestWhite
contact affiliation	Department of Biological Engineering, MIT
contact email	fwhite@mit.edu
lab head
LaurenStopfer
contact affiliation	MIT
contact email	lstopfer@mit.edu
dataset submitter

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://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD029884

PRIDE project URI

• PRIDE
  1. PXD029884
     1. Label: PRIDE project
     2. Name: MEK inhibition enhances presentation of targetable MHC-I tumor antigens in mutant melanomas - targeted data