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

Autor: 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
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Molecular Therapy: Oncolytics, Vol 21, Iss , Pp 315-328 (2021)
Druh dokumentu: article
ISSN: 2372-7705
DOI: 10.1016/j.omto.2021.04.009
Popis: 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.
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