ArticleCancer immunology, immunotherapy : CII2019
Editing the immunopeptidome of melanoma cells using a potent inhibitor of endoplasmic reticulum aminopeptidase 1 (ERAP1).
Article in Cancer immunology, immunotherapy : CII, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
- Review
- Five dominant amino acid substitution signatures shape tumour immunity.Molecular systems biology · 2026Article
- Messing with Signal 1: How Perturbed MHC Class I Antigen Presentation Contributes to Cancer.Cells · 2026Review
- ERAP1 Allotypes 2 and 10 Differentially Regulate the Immunopeptidome of Melanocytes.Immunology · 2026Article
- Defects in antigen processing and presentation: mechanisms, immune evasion and implications for cancer vaccine development.Nature reviews. Immunology · 2026Review
- Methods for Isolating and Analyzing the HLA Class I Immunopeptidome.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Non-Canonical, Strongly Selective Protein Disulfide Isomerases as Anticancer Therapeutic Targets.Biomolecules · 2025Review
- ERAP1 Activity Modulates the Immunopeptidome but Also Affects the Proteome, Metabolism, and Stress Responses in Cancer Cells.Molecular & cellular proteomics : MCP · 2025Article
- Combining ERAP1 silencing and entinostat therapy to overcome resistance to cancer immunotherapy in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2024Article
- ERAP Inhibitors in Autoimmunity and Immuno-Oncology: Medicinal Chemistry Insights.Journal of medicinal chemistry · 2024Review
- The Role of Aminopeptidase ERAP1 in Human Pathology-A Review.Current issues in molecular biology · 2024Review
- Non-mutational neoantigens in disease.Nature immunology · 2024Review
- The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I-Associated Peptides.Cancer immunology research · 2023Article
- Phosphinic Peptides as Tool Compounds for the Study of Pharmacologically Relevant Zn-Metalloproteases.ACS pharmacology & translational science · 2022Review
- Article
- IntroSpect: Motif-Guided Immunopeptidome Database Building Tool to Improve the Sensitivity of HLA I Binding Peptide Identification by Mass Spectrometry.Biomolecules · 2022Article
- ERAP2 Inhibition Induces Cell-Surface Presentation by MOLT-4 Leukemia Cancer Cells of Many Novel and Potentially Antigenic Peptides.International journal of molecular sciences · 2022Article
- The ER Aminopeptidases, ERAP1 and ERAP2, synergize to self-modulate their respective activities.Frontiers in immunology · 2022Article
- Endoplasmic Reticulum Aminopeptidase 1 Is Involved in Anti-viral Immune Response of Hepatitis B Virus by Trimming Hepatitis B Core Antigen to Generate 9-Mers Peptides.Frontiers in microbiology · 2022Article
- Targeting the antigen processing and presentation pathway to overcome resistance to immune checkpoint therapy.Frontiers in immunology · 2022Review
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
The efficacy of cancer immunotherapy, including treatment with immune-checkpoint inhibitors, often is limited by ineffective presentation of antigenic peptides that elicit T-cell-mediated anti-tumor cytotoxic responses. Manipulation of antigen presentation pathways is an emerging approach for enhancing the immunogenicity of tumors in immunotherapy settings. ER aminopeptidase 1 (ERAP1) is an intracellular enzyme that trims peptides as part of the system that generates peptides for binding to MHC class I molecules (MHC-I). We hypothesized that pharmacological inhibition of ERAP1 in cells could regulate the cellular immunopeptidome. To test this hypothesis, we treated A375 melanoma cells with a recently developed potent ERAP1 inhibitor and analyzed the presented MHC-I peptide repertoire by isolating MHC-I, eluting bound peptides, and identifying them using capillary chromatography and tandem mass spectrometry (LC-MS/MS). Although the inhibitor did not reduce cell-surface MHC-I expression, it induced qualitative and quantitative changes in the presented peptidomes. Specifically, inhibitor treatment altered presentation of about half of the total 3204 identified peptides, including about one third of the peptides predicted to bind tightly to MHC-I. Inhibitor treatment altered the length distribution of eluted peptides without change in the basic binding motifs. Surprisingly, inhibitor treatment enhanced the average predicted MHC-I binding affinity, by reducing presentation of sub-optimal long peptides and increasing presentation of many high-affinity 9-12mers, suggesting that baseline ERAP1 activity in this cell line is destructive for many potential epitopes. Our results suggest that chemical inhibition of ERAP1 may be a viable approach for manipulating the immunopeptidome of cancer.
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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.