To TAP or not to TAP: alternative peptides for immunotherapy of cancer. (June 2020) - Marijt, Koen A.
Highlights: TAP function is often abrogated in malignant and virus-infected cells. TAP-deficiency allows presentation of an alternative immunopeptidome. TAP-independent peptides are predominantly derived from signal sequences and C-terminal 'tails'. TAP-independent peptides are potential tumor antigens for immunotherapy. Abstract : Intracellular processing of antigens is crucial for the generation of T cell immunity towards cancers, since cleaved protein products are the molecular targets of these adaptive lymphocytes. The majority of antigenic peptides requires the TAP transporter to gain access to the peptide loading complex in the ER lumen where they bind MHC class I (MHC-I). This pivotal role of TAP in antigen processing makes the system vulnerable for modifications in cancer cells and indeed human cancers frequently silence this gene epigenetically. Interestingly, TAP-independent processing pathways then become apparent and partly restore MHC class I presentation with alternative peptides. In this review we discuss recent insights on how TAP-independent processing of immunogenic peptides occurs, and how these antigens can be exploited for cancer immunotherapy.