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-MS2 profiling 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).