Oral Presentation 23rd Annual Lorne Proteomics Symposium 2018

nUPLC-MS2 profiling of class I immunopeptidomes of HLA-A2-positive breast cancer patients prioritises antigen selection for tumour-specific immunotherapy (#10)

Nicola Ternette 1 2 , Marloes Olde-Nordkamp 3 , Julius Muller 1 , Amanda Anderson 3 , Annalisa Nicastri 2 , Adrian VS Hill 1 , Benedikt Kessler 2 , Demin Li 3
  1. Jenner Institute, University of Oxford, Oxford, UK
  2. Target Discovery Institute, University of Oxford, Oxford, UK
  3. Nuffied Department of Clinical Laboratory Sciences, University of Oxford, Oxford, UK

The success of immune checkpoint inhibition in the treatment of cancer patients demonstrates the potency of utilizing T cell reactivity for cancer therapy. However, varying results between individual patients and severe side-effects highlight the need to increase treatment specificity. Here, we have analysed the immunopeptidomic landscape of 6 HLA-A2-positive triple negative breast cancer (TNBC) patients by nano-ultra performance liquid chromatography tandem mass spectrometry (nUPLC-MS2) in order to identify tumour-specific antigens that could be used as targets for T-cell mediated therapy. nUPLC-MSprofiling  identified a total of 35,775 peptide sequences from cancer and adjacent normal tissues. 139 shared, tumour-enriched HLA-peptide sequences predicted to bind HLA-A*0201 were identified in the cohort. Three HLA-peptides that were presented in tumours of all patients originated from Syntenin-1, a protein that is known to be highly expressed in breast cancer cell lines, and is associated with breast cancer progression1,2, making it an attractive target for immunotherapy in A2-positive patients. We further shortlisted the most relevant tumour-specific source proteins that are presented across the cohort by introducing an average tumour-enhanced cohort presentation coverage (aTeCC), and identified Cofilin-1 (CFL-1), Interleukin-32 (IL-32), Proliferating cell nuclear antigen (PCNA), and Syntenin-1 as antigens with the highest aTeCC values, prioritizing these antigens as targets for immunotherapeutic approaches to breast cancer.

1          Yang, Y. et al. Elevated expression of syntenin in breast cancer is correlated with lymph node metastasis and poor patient survival. Breast Cancer Res 15, R50, doi:10.1186/bcr3442 (2013).

2          Koo, T. H. et al. Syntenin is overexpressed and promotes cell migration in metastatic human breast and gastric cancer cell lines. Oncogene 21, 4080-4088, doi:10.1038/sj.onc.1205514 (2002).