Lightning Oral Talk 25th Annual Lorne Proteomics Symposium 2020

Multi-omic analysis reveals the pro-inflammatory cytokine IFNγ modulates the immunopeptidome of triple negative breast cancer cells. (#24)

Gabriel Goncalves 1 , Kerry Mullan 1 , Divya Duscharla 1 , Rochelle Ayala 1 , Ethan Passantino 1 , Nicole Mifsud 1 , Nathan Croft 1 , Pouya Faridi 1 , Anthony Purcell 1
  1. Department of Biochemistry and Molecular Biology, Monash University , Clayton, Victoria , Australia

The heterogeneous nature of Triple-Negative Breast Cancer (TNBC) has highlighted the need for novel approaches in treatment. Recent studies demonstrate the feasibility of a peptide vaccination approach to induce T-cell mediated killing of cancerous cells. To identify potential T-cell targets we used the TNBC model cell line MDA-MB-231 and examined cell surface peptides (immunopeptidome) being presented by human leukocyte antigen (HLA) complexes after treatment with the pro-inflammatory cytokine interferon-γ (IFNγ) and related these findings to changes in the cellular transcriptome and proteome. Using high resolution mass spectrometry, we identified a total of 82,915 peptides from 9,553 source proteins were presented across HLA-I and HLA-II alleles and observed considerable remoulding of the immunopeptidome upon cytokine stimulation. We then examined the correlation between the 10,248 quantified transcripts and 6,784 quantified proteins following IFNγ treatment and found 229 differentially expressed proteins many of which were involved in the pathway of antigen presentation. These results highlighted a high degree of plasticity in the immunopeptidome caused by cytokine stimulation of TNBC. Of note, IFNγ increased the diversity and abundance of the peptide repertoire as a result of changes in the antigen presentation machinery rather than changes in transcript and protein abundance. This suggests that under pro-inflammatory conditions a greater variety of potential T cell targets are unveiled to the immune system. This has important implications for the development of personalised cancer vaccination strategies.