Immunopeptidomic Profiling of HLA-A2-Positive Triple Negative Breast Cancer Identifies Potential Immunotherapy Target Antigens.
Ternette N., Olde Nordkamp MJM., Muller J., Anderson AP., Nicastri A., Hill AVS., Kessler BM., Li D.
The recent development in immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cells in the treatment of cancer has not only demonstrated the potency of utilising T-cell reactivity for cancer therapy, but has also highlighted the need for developing new approaches to discover targets suitable for such novel therapeutics. Here we analysed the immunopeptidomes of 6 HLA-A2-positive triple negative breast cancer (TNBC) samples by nano-ultra performance liquid chromatography tandem mass spectrometry (nUPLC-MS2 ). Immunopeptidomic profiling identified a total of 19,675 peptides from tumour and adjacent normal tissue and 130 of the peptides were found to have higher abundance in tumour than in normal tissues. To determine potential therapeutic target proteins, we calculated the average tumour-associated cohort coverage (aTaCC) that represents the percentage coverage of each protein in this cohort by peptides that had higher tumourial abundance. Cofilin-1 (CFL-1), interleukin-32 (IL-32), proliferating cell nuclear antigen (PCNA), syntenin-1 (SDCBP) and ribophorin-2 (RPN-2) were found to have the highest aTaCC scores. We propose that these antigens could be evaluated further for their potential as targets in breast cancer immunotherapy and the small cohort immunopeptidomics analysis technique could be used in the wide spectrum of target discovery. This article is protected by copyright. All rights reserved.