Palmitoylated antigens for the induction of anti-tumor CD8+ T cells and enhanced tumor recognition
| Autor: | Sandra J. van Vliet, Juan J. Garcia-Vallejo, Sjoerd T.T. Schetters, Martino Ambrosini, Eelco D. Keuning, Rieneke van de Ven, Sophie K. Horrevorts, Sanne Duinkerken, Tanja D. de Gruijl, Hakan Kalay, Laura J.W. Kruijssen, Dorian A. Stolk, Yvette van Kooyk |
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| Přispěvatelé: | Medical oncology laboratory, Molecular cell biology and Immunology, Otolaryngology / Head & Neck Surgery, CCA - Cancer biology and immunology, AII - Cancer immunology |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research dendritic cell Priming (immunology) chemical and pharmacologic phenomena Major histocompatibility complex 03 medical and health sciences 0302 clinical medicine antigen Antigen MHC class I palmitic acid Cytotoxic T cell Pharmacology (medical) anti-tumor peptide modification RC254-282 biology Chemistry Neoplasms. Tumors. Oncology. Including cancer and carcinogens Dendritic cell tumor recognition vaccination Cell biology CTL 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Molecular Medicine mono-palmitoylation Original Article CD8 antigen enrichment |
| Zdroj: | Molecular Therapy: Oncolytics, Vol 21, Iss, Pp 315-328 (2021) Stolk, D A, Horrevorts, S K, Schetters, S T T, Kruijssen, L J W, Duinkerken, S, Keuning, E, Ambrosini, M, Kalay, H, van de Ven, R, Garcia-Vallejo, J J, de Gruijl, T D, van Vliet, S J & van Kooyk, Y 2021, ' Palmitoylated antigens for the induction of anti-tumor CD8+ T cells and enhanced tumor recognition ', Molecular Therapy-Oncolytics, vol. 21, pp. 315-328 . https://doi.org/10.1016/j.omto.2021.04.009 Molecular Therapy-Oncolytics, 21, 315-328. Nature Publishing Group Molecular Therapy Oncolytics |
| 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. Graphical abstract A dual loading vaccination strategy with palmitoylated peptides is developed to induce robust anti-tumor immunity. Dendritic cells are loaded with palmitoylated peptides to activate antigen-specific T cells, while tumor cells are loaded with palmitoylated peptides to present epitopes for enhanced recognition by antigen-specific T cells. |
| Databáze: | OpenAIRE |
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