The identification of immunotherapeutic candidates via canonical and non-canonical HLA pathways in Triple Negative Breast Cancer

This study examined how the immune cytokine IFNγ affects triple negative breast cancer (TNBC) cells, focusing on peptides presented by HLA molecules on the cell surface to be used for immunotherapies. Using mass spectrometry, we identified ~85,000 peptides and found that IFNγ enhances increases the diversity and plasticity of HLA peptides. Notably, HLA-E was consistently up-regulated. To study HLA-E peptides, three methods were developed, identifying over 1,000 potential peptide targets. Many of these peptides come from tumour antigens, making them suitable for immunotherapy. This research highlights the potential for HLA-E-based therapies in TNBC, which could be universally applied due to the monomorphic nature of HLA-E.