Cited by 109vaccines and immunoinformatics approachesAdvanced Proteomics Techniques and ApplicationsCancer Immunotherapy and Biomarkers

Multiplexed relative and absolute quantitative immunopeptidomics reveals MHC I repertoire alterations induced by CDK4/6 inhibition

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Stopfer, Lauren E., Mesfin, Joshua M., Joughin, Brian A., Lauffenburger, Douglas A., White, Forest M.·2020·Nature Communications

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Abstract

Peptides bound to class I major histocompatibility complexes (MHC) play a critical role in immune cell recognition and can trigger an antitumor immune response in cancer. Surface MHC levels can be modulated by anticancer agents, altering immunity. However, understanding the peptide repertoire's response to treatment remains challenging and is limited by quantitative mass spectrometry-based strategies lacking normalization controls. We describe an experimental platform that leverages recombinant heavy isotope-coded peptide MHCs (hipMHCs) and multiplex isotope tagging to quantify peptide repertoire alterations using low sample input. HipMHCs improve quantitative accuracy of peptide repertoire changes by normalizing for variation across analyses and enable absolute quantification using internal calibrants to determine copies per cell of MHC antigens, which can inform immunotherapy design. Applying this platform in melanoma cell lines to profile the immunopeptidome response to CDK4/6 inhibition and interferon-γ - known modulators of antigen presentation - uncovers treatment-specific alterations, connecting the intracellular response to extracellular immune presentation.

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  • The MHC class I peptidome of human melanoma cells treated with palbociclib is enriched for tumor-associated antigens and peptides from E2F target proteins involved in cell cycle blockage.

    “the MHC class I peptidome of human melanoma cells exposed to the CDK4/CDK6 inhibitor palbociclib is enriched for tumor-associated antigens (TAAs) and peptides from E2F target proteins that are directly implicated in cell cycle blockage (Stopfer et al., 2020).”

    From Immunomodulation by targeted anticancer agents (2021) · cites this paper as Stopfer et al., 2020

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  1. [66]Crooks GE Hon G Chandonia JM Brenner SE WebLogo: a sequence logo generator Genome Res. 2004 14 1188 1190 15173120 PMC419797

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Authors
Stopfer, L. E., Mesfin, J. M., Joughin, B. A., Lauffenburger, D. A., & White, F. M.
Affiliations
  • Koch Institute for Integrative Cancer Research At MIT (US)
  • Massachusetts Institute of Technology (US)
Corresponding author
White, Forest M.
Venue
Nature Communications
Published
2020-06-02
Volume
11
Issue
1
Pages
2760-2760
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3031716951
Cited by
109
References
79
Citations by year
2026: 17 · 2025: 21 · 2024: 11 · 2023: 23 · 2022: 14 · 2021: 16 · 2020: 6 · 2019: 1
FWCI
4.76
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
Funders
  • Melanoma Research Alliance (565436)
  • Array BioPharma
  • Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
  • National Institutes of Health (CA210180)
  • National Heart, Lung, and Blood Institute (T32HL105373)
  • National Cancer Institute (U54CA210180, P30CA014051)
  • National Institute of Environmental Health Sciences (T32ES007020)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
immunopeptidomics, CDK4/6 inhibition, absolute quantification, melanoma, interferon-gamma, antigen presentation, cancer immunotherapy
MeSH terms
Antigens, Cell Line, Humans, Immunotherapy, Interferon-gamma, Peptides, Mass Spectrometry, Histocompatibility Antigens Class I, Antigen Presentation, Proteomics, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6

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