To this end, and to interrogate potential alterations in antigen processing and presentation, we used quantitative mass spectrometry (MS)-based proteomic analysis to globally profile the landscape of human leucocyte antigen (HLA) Class I-presented immunopeptidome, the total proteome, and the Class I-interactome in EGFR-mutant lung adenocarcinoma cell lines and isogenic osimertinib-resistant (OsiR) counterparts. Here, EGFR is linked to lung adenocarcinoma.