20.500.12556/RUL-158422 Factor of time in dendritic cell (DC) maturation short-term activation of DCs significantly improves type 1 cytokine production and T cell responses Dendritic cells (DCs) have been intensively studied in correlation to tumor immunology and for the development DC-based cancer vaccines. Here, we present the significance of the temporal aspect of DC maturation for the most essential subsequent timepoint, namely at interaction with responding T cells or after CD40-Ligand restimulation. Mostly, DC maturation is still being achieved by activation processes which lasts 24 h to 48 h. We hypothesized this amount of time is excessive from a biological standpoint and could be the underlying cause for functional exhaustion. Indeed, shorter maturation periods resulted in extensive capacity of monocyte-derived DCs to produce inflammatory cytokines after re-stimulation with CD40-Ligand. This effect was most evident for the primary type 1 polarizing cytokine, IL-12p70. This capacity reached peak at 6 h and dropped sharply with longer exposure to initial maturation stimuli (up to 48 h). The 6 h maturation protocol reflected superiority in subsequent functionality tests. Namely, DCs displayed twice the allostimulatory capacity of 24 h- and 48 h-matured DCs. Similarly, type 1 T cell response measured by IFN-γ production was 3-fold higher when CD4$^+$ T cells had been stimulated with shortly matured DC and over 8-fold greater in case of CD8$^+$ T cells, compared to longer matured DCs. The extent of melanoma-specific CD8$^+$ cytotoxic T cell induction was also greater in case of 6 h DC maturation. The major limitation of the study is that it lacks in vivo evidence, which we aim to examine in the future. Our findings show an unexpectedly significant impact of temporal exposure to activation signals for subsequent DC functionality, which we believe can be readily integrated into existing knowledge on in vitro/ex vivo DC manipulation for various uses. We also believe this has important implications for DC vaccine design for future clinical trials. dendritic cells maturation vaccines cytotoxic T cells cancer anti-tumor responses dendritične celice zorenje citotoksične celice T protitumorski odzivi rak (medicina) cepiva true false true Angleški jezik Slovenski jezik Članek v reviji 2024-06-10 09:02:02 2024-06-10 09:02:10 2024-06-27 03:21:01 0000-00-00 00:00:00 2024 0 0 Str. 14 str. art. 541 Vol. 22 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.371:616-006 1479-5876 10.1186/s12967-024-05368-4 198061059 s12967-024-05368-4_(2).pdf s12967-024-05368-4_(2).pdf 1 69F0E7A791E46A8047BF7B43E8A6B5A4 494cfd13ae38f4bd2b7c6fbe74fdaeb06b0d719d552feedaa73d13770e09f415 de0c7ff5-26f8-11ef-8889-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=186029 https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05368-4 1 5ba53844-26f7-11ef-8889-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=186027 Fakulteta za farmacijo 0 0 0