التفاصيل البيبلوغرافية
| العنوان: |
Combined TLR-3/TLR-8 Signaling in the Presence of α-Type-1 Cytokines Represents a Novel and Potent Dendritic Cell Type-1, Anti-Cancer Maturation Protocol |
| المؤلفون: |
Tadej Fevžer, Primož Poženel, Kaja Zajc, Nataša Tešić, Urban Švajger |
| المصدر: |
Cells, Vol 11, Iss 5, p 835 (2022) |
| بيانات النشر: |
MDPI AG, 2022. |
| سنة النشر: |
2022 |
| المجموعة: |
LCC:Cytology |
| مصطلحات موضوعية: |
dendritic cells, maturation, type-1 polarization, cytotoxic T cells, Cytology, QH573-671 |
| الوصف: |
During the ex vivo generation of anti-cancer dendritic cell (DC)-based vaccines, their maturation still represents one of the most crucial steps of the manufacturing process. A superior DC vaccine should: possess extensive expression of co-stimulatory molecules, have an exceptional type-1 polarization capacity characterized by their ability to produce IL-12p70 upon contact with responding T cells, migrate efficiently toward chemokine receptor 7 (CCR7) ligands, and have a superior capacity to activate cytotoxic T cell responses. A major advance has been achieved with the discovery of the next generation maturation protocol involving TLR-3 agonist (poly I:C), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, and IFN-α, and has since been known as α-type-1 maturation cocktail. We demonstrate how this combination can be greatly enhanced by the inclusion of a TLR-8 stimulation (R848), thereby contributing to potentiation between different TLR signaling pathways. For maximum efficiency, TLR-3 stimulation should precede (termed pre I:C) the stimulation with the R848/TNF-α/IL-1β/IFN-α/IFN-γ cocktail. When compared to DCs matured with α-type-1 maturation cocktail (αDCs), DCs matured with pre I:C/R848/TNF-α/IL-1β/IFN-α/IFN-γ (termed zDCs) displayed higher expression of CD80 and CD86 co-stimulatory molecules. Importantly, after CD40-ligand stimulation, which simulates DC-T cell contact, zDCs were much more proficient in IL-12p70 production. In comparison to αDCs, zDCs also displayed a significantly greater migratory capacity toward chemokine ligands (CCL)19 and CCL21, and had a significantly greater allo-stimulatory capacity. Finally, zDCs were also superior in their capacity to induce melanoma-specific CD8+ T cells, CD8+ T cell proliferation, and cytotoxic T cells, which produced approximately two times more IFN-γ and more granzyme B, than those stimulated with αDCs. In conclusion, we present a novel and superior DC maturation cocktail that could be easily implemented into next generation DC vaccine manufacturing protocols in future trials. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2073-4409 |
| Relation: |
https://www.mdpi.com/2073-4409/11/5/835; https://doaj.org/toc/2073-4409 |
| DOI: |
10.3390/cells11050835 |
| URL الوصول: |
https://doaj.org/article/b48f182ddb1f4f8cb95395c107dca292 |
| رقم الانضمام: |
edsdoj.b48f182ddb1f4f8cb95395c107dca292 |
| قاعدة البيانات: |
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