Palmitoylated antigens for the induction of anti-tumor CD8+ T cells and enhanced tumor recognition

Dorian A. Stolk, Sophie K. Horrevorts, Sjoerd T. T. Schetters, Laura J. W. Kruijssen, Sanne Duinkerken, Eelco Keuning, Martino Ambrosini, Hakan Kalay, Rieneke van de Ven, Juan J. Garcia-Vallejo, Tanja D. de Gruijl, Sandra J. van Vliet, Yvette van Kooyk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Induction of tumor-specific cytotoxic CD8+ T cells (CTLs) via immunization relies on the presentation of tumor-associated peptides in major histocompatibility complex (MHC) class I molecules by dendritic cells (DCs). To achieve presentation of exogenous peptides into MHC class I, cytosolic processing and cross-presentation are required. Vaccination strategies aiming to induce tumor-specific CD8+ T cells via this exogenous route therefore pose a challenge. In this study, we describe improved CD8+ T cell induction and in vivo tumor suppression of mono-palmitic acid-modified (C16:0) antigenic peptides, which can be attributed to their unique processing route, efficient receptor-independent integration within lipid bilayers, and continuous intracellular accumulation and presentation through MHC class I. We propose that this membrane-integrating feature of palmitoylated peptides can be exploited as a tool for quick and efficient antigen enrichment and MHC class I loading. Importantly, both DCs and non-professional antigen-presenting cells (APCs), similar to tumor cells, facilitate anti-tumor immunity by efficient CTL priming via DCs and effective recognition of tumors through enhanced presentation of antigens.
Original languageEnglish
Pages (from-to)315-328
Number of pages14
JournalMolecular Therapy - Oncolytics
Volume21
DOIs
Publication statusPublished - 25 Jun 2021

Cite this