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Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
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Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model

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Immunopeptidomic Profiling of HLA-A2-Positive Triple Negative Breast Cancer Identifies Potential Immunotherapy Target

Nicola Ternette1,2, Marloes J M Olde Nordkamp3, Julius Müller1

  • 1The Jenner Institute, University of Oxford, Oxford, OX3 7FZ, UK.

Proteomics
|May 23, 2018
PubMed

Insights

New immunotherapies like CAR T-cells need novel targets. This study identified five potential breast cancer targets, Cofilin-1, IL-32, PCNA, syntenin-1, and ribophorin-2, using immunopeptidomics.

Area of Science:

  • Oncology
  • Immunology
  • Proteomics

Background:

  • Advances in cancer immunotherapy, including immune checkpoint inhibitors and CAR T-cells, highlight the need for novel therapeutic targets.
  • Identifying specific tumor antigens is crucial for developing effective T-cell-based cancer therapies.

Purpose of the Study:

  • To discover potential therapeutic targets for breast cancer immunotherapy by analyzing tumor immunopeptidomes.
  • To evaluate the utility of small cohort immunopeptidomics for antigen discovery.

Main Methods:

  • Analysis of immunopeptidomes from six HLA-A2-positive triple-negative breast cancer (TNBC) samples using nano-ultra performance liquid chromatography tandem mass spectrometry (nUPLC-MS²).
  • Quantification of peptide abundance in tumor versus adjacent normal tissues.
  • Calculation of average tumor-associated cohort coverage (aTaCC) to identify highly abundant tumor-specific peptides.

Main Results:

  • A total of 19,675 peptides were identified, with 130 peptides showing higher abundance in tumor tissues.
  • Cofilin-1 (CFL-1), interleukin-32 (IL-32), proliferating cell nuclear antigen (PCNA), syntenin-1 (SDCBP), and ribophorin-2 (RPN-2) exhibited the highest aTaCC scores.
  • These proteins represent promising candidates for breast cancer immunotherapy targets.

Conclusions:

  • The identified proteins (CFL-1, IL-32, PCNA, SDCBP, RPN-2) warrant further investigation as potential targets for breast cancer immunotherapy.
  • Small cohort immunopeptidomics is a viable technique for discovering novel cancer antigens.
  • The study provides a valuable dataset (ProteomeXchange identifier PXD009738) for future research.
Keywords:
HLA-A2aTaCCbreast cancerimmunopeptidomemass spectrometry

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