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

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 (MHC-I), cytosolic processing and cross-presentation is required. Vaccination strategies aiming to induce tumor-specific CD8+ T-cells via this exogenous route, therefore pose a challenge. Here, 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-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-I loading. Importantly, both DCs and non-professional APCs, like tumor cells, facilitate anti-tumor immunity by efficient CTL priming via DCs and effective recognition of tumors through enhanced presentation of antigens.