PXD029860

PXD029860 is an original dataset announced via ProteomeXchange.

Title	MEK inhibition enhances presentation of targetable MHC-I tumor antigens in mutant melanomas
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	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:40:30.988.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD029860
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Lauren Stopfer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-22 01:19:50	ID requested
1	2023-03-11 02:11:59	announced
⏵ 2	2023-11-14 08:40:31	announced	2023-11-14: Updated project metadata.

10.6019/PXD029860;

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,MHC, immunopeptidomics, antigen presentation

Forest White
contact affiliation	Koch Institute of Integrative Cancer Research, MIT, Cambridge, MA 02139
contact email	fwhite@mit.edu
lab head
Lauren Stopfer
contact affiliation	MIT
contact email	lstopfer@mit.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029860
     1. Label: PRIDE project
     2. Name: MEK inhibition enhances presentation of targetable MHC-I tumor antigens in mutant melanomas