ArticleProceedings of the National Academy of Sciences of the United States of America2022
MEK inhibition enhances presentation of targetable MHC-I tumor antigens in mutant melanomas.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- CTMP-REV7 axis modulates MHC-I antigen presentation via CDK1-AKT crosstalk in MSI-L/MSS colorectal cancer.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- AI-enabled virtual immunopeptidomics links quantitative neoantigen presentation to immunogenicity.bioRxiv : the preprint server for biology · 2026Article
- Novel Syngeneic Cell Lines for Studying High-Risk BRAFV600E-Driven Colorectal Cancer In Vivo.Cancer research communications · 2026Article
- Review
- MHC1-TIP enables single-tube multimodal immunopeptidome profiling and uncovers intratumoral heterogeneity in antigen presentation.Communications biology · 2026Article
- Zapnometinib treatment and influenza A virus infection modulate the HLA class I ligandome in human lung adenocarcinoma cells.Frontiers in immunology · 2026Article
- Programmed cell death evasion in BRAF V600E-driven primary CNS tumors and thyroid cancer brain metastases.Frontiers in neurology · 2026Review
- Scaling Large Language Models for Next-Generation Single-Cell Analysis.bioRxiv : the preprint server for biology · 2026Article
- Immune microenvironment evolution across the serrated neoplasia pathway and its relevance to immunotherapy.Frontiers in oncology · 2026Review
- Engineered antibodies that stabilize drug-modified KRASNature communications · 2025Article
- Wild-type KRAS activation drives evasion of interferon-mediated immunity and resistance to immunotherapy in hepatocellular carcinoma.Nature communications · 2025Article
- Targeting infection-specific peptides in immunopeptidomics studies for vaccine target discovery.The Journal of experimental medicine · 2025Article
- Targeting gut microbiota and arginase boosts MEK inhibitors' enhancement of antitumour immunity via MHC-I upregulation in colorectal cancer.British journal of cancer · 2025Article
- Therapeutic Opportunities in Melanoma Through PRAME Expression.Biomedicines · 2025Review
- Comet Fragment-Ion Indexing for Enhanced Peptide Sequencing.Journal of proteome research · 2025Article
- Elucidating Ras protein as a dual therapeutic target for inflammation and cancer: a review.Discover oncology · 2025Review
- A heterogeneous pharmaco-transcriptomic landscape induced by targeting a single oncogenic kinase.bioRxiv : the preprint server for biology · 2025Article
- Validation and quantification of peptide antigens presented on MHCs using SureQuant.Nature protocols · 2025Review
- Investigative needle core biopsies support multimodal deep-data generation in glioblastoma.Nature communications · 2025Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Combining multiple therapeutic strategies in NRAS/BRAF mutant melanoma-namely MEK/BRAF kinase inhibitors, immune checkpoint inhibitors (ICIs), 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 (MEKi) alters anti-tumor immunity by utilizing quantitative immunopeptidomics to profile changes in the peptide major histocompatibility molecules (pMHC) repertoire. These data reveal a collection of tumor antigens whose presentation levels are selectively augmented following therapy, including several epitopes present at over 1,000 copies per cell. We leveraged the tunable abundance of MEKi-modulated antigens by targeting four 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.