Prostaglandin E\(_2\) in a TLR3‑ and 7/8‑agonist‑based DC maturation cocktail generates mature, cytokine‑producing, migratory DCs but impairs antigen cross‑presentation to CD8\(^+\) T cells
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-232311
- Mature dendritic cells (DCs) represent cellular adjuvants for optimal antigen presentation in cancer vaccines. Recently, a combination of prostaglandin E\(_2\) (PGE\(_2\)) with Toll-like receptor agonists (TLR-P) was proposed as a new standard to generate superior cytokine-producing DCs with high migratory capacity. Here, we compare TLR-P DCs with conventional DCs matured only with the proinflammatory cytokines TNFα and IL-1ß (CDCs), focussing on the interaction of resulting DCs with CD8\(^+\) T-cells. TLR-P matured DCs showed elevatedMature dendritic cells (DCs) represent cellular adjuvants for optimal antigen presentation in cancer vaccines. Recently, a combination of prostaglandin E\(_2\) (PGE\(_2\)) with Toll-like receptor agonists (TLR-P) was proposed as a new standard to generate superior cytokine-producing DCs with high migratory capacity. Here, we compare TLR-P DCs with conventional DCs matured only with the proinflammatory cytokines TNFα and IL-1ß (CDCs), focussing on the interaction of resulting DCs with CD8\(^+\) T-cells. TLR-P matured DCs showed elevated expression of activation markers such as CD80 and CD83 compared to CDCs, together with a significantly higher migration capacity. Secretion of IL-6, IL-8, IL-10, and IL-12 was highest after 16 h in TLR-P DCs, and only TLR-P DCs secreted active IL-12p70. TLR-P DCs as well as CDCs successfully primed multifunctional CD8\(^+\) T-cells from naïve precursors specific for the peptide antigens Melan-A, NLGN4X, and PTP with comparable priming efficacy and T-cell receptor avidity. CD8\(^+\) T-cells primed by TLR-P DCs showed significantly elevated expression of the integrin VLA-4 and a trend for higher T-cell numbers after expansion. In contrast, TLR-P DCs displayed a substantially reduced capability to cross-present CMVpp65 protein antigen to pp65-specific T cells, an effect that was dose-dependent on PGE2 during DC maturation and reproducible with several responder T-cell lines. In conclu-sion, TLR-P matured DCs might be optimal presenters of antigens not requiring processing such as short peptides. However, PGE\(_2\) seems less favorable for maturation of DCs intended to process and cross-present more complex vaccine antigens such as lysates, proteins or long peptides.…
Autor(en): | Philipp Gierlich, Veronika Lex, Antje Technau, Anne Keupp, Lorenz Morper, Amelie Glunz, Hanno Sennholz, Johannes Rachor, Sascha Sauer, Ana Marcu, Götz Ulrich Grigoleit, Matthias Wölfl, Paul G. Schlegel, Matthias EyrichORCiD |
---|---|
URN: | urn:nbn:de:bvb:20-opus-232311 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Kinderklinik und Poliklinik |
Medizinische Fakultät / Medizinische Klinik und Poliklinik II | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Cancer Immunology, Immunotherapy |
ISSN: | 0340-7004 |
Erscheinungsjahr: | 2020 |
Band / Jahrgang: | 69 |
Seitenangabe: | 1029–1042 |
Originalveröffentlichung / Quelle: | Cancer Immunology, Immunotherapy (2020) 69:1029–1042 https://doi.org/10.1007/s00262-019-02470-1 |
DOI: | https://doi.org/10.1007/s00262-019-02470-1 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | TLR agonists; cancer vaccines; dendritic cells; prostaglandin E2; tumor-specific CD8+ T cells |
Datum der Freischaltung: | 18.05.2021 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |