Birinapant reshapes tumor immunopeptidome and enhances antigen presentation

Major histocompatibility complex proteins present peptides for immune surveillance and are crucial for the recognition of infected or tumor cells by T lymphocytes. Cancer testis antigen peptides and neoantigens are effective targets and can be directly identified by immunopeptidomics based on mass spectrometry. Birinapant, an antagonist of Inhibitor of Apoptosis Proteins, upregulates MHCs in tumor cells and displays a better tumoricidal effect when used in combination with immune checkpoint inhibitors, indicating that Birinapant may affect the antigen presentation pathway; however, the specific mechanism remains elusive. Based on high resolution mass spectrometry and in vitro and in vivo models, we adopted integrated genomics, proteomics, and immunopeptidomics strategies to study the mechanism underlying the regulation of tumor immunity by Birinapant from the perspective of antigen presentation.So we used whole exome sequencing to obtain mutation information of cell lines HT29 and MCF7, than constructed specific proteins database for subsequent immunopeptidomics and discovery of neoantigens.