Bojan Pavlović1, Sergej Tomić2, Jelena Đokić2, Saša Vasilijić3, Dragana Vučević3, Jovanka Lukić4, Alisa Gruden-Movsesijan5, Nataša Ilić5, Milan Marković6, Miodrag Čolić7. 1. Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia. 2. Medical Faculty of the Military Medical Academy, University of Defence, Belgrade, Serbia. 3. Institute for Medical Research, Military Medical Academy, University of Defence, Belgrade, Serbia. 4. Institute for Molecular Genetics and Genetic Engineering, Laboratory for Molecular Microbiology, University of Belgrade, Belgrade, Serbia. 5. Institute for the Application of Nuclear Energy, University of Belgrade, Belgrade, Serbia. 6. Medical Faculty of the Military Medical Academy, University of Defence, Belgrade, Serbia; Medical Faculty, University of Niš, Niš, Serbia. 7. Medical Faculty of the Military Medical Academy, University of Defence, Belgrade, Serbia; Medical Faculty, University of Niš, Niš, Serbia. Electronic address: mjcolic@eunet.rs.
Abstract
BACKGROUND AIMS: Because of the labor-intensive and time-consuming conventional protocols for the generation of dendritic cells (DCs) as the most promising tools for anti-cancer therapy that enable the induction of a T-helper (Th)1-mediated anti-tumor immune response, the use of short-term protocols has been proposed. However, data on the applicability of such protocols in cancer immunotherapy are quite limited. METHODS: We compared the phenotypic and functional capability of fast DCs (fDCs) differentiated for 24 h and then matured for 48 h with Poly (I:C), a strong Th1-promoting agent, with donor-matched conventional DCs (cDCs) differentiated for 5 days and matured likewise. RESULTS: Of 12 donors tested, we identified seven whose monocytes failed to develop into immunogenic DCs through the use of fDC protocol, on the basis of incomplete downregulation of CD14, low expression of CD1a and macrophage-like morphology. Such fDCs have significantly lower expression of CD83, CD86, CCR7 and CD40, weaker allo-stimulatory Th1- and Th17-polarizing capacity caused by poor production of interleukin (IL)-12p70 and IL-23 and high production of IL-10, and prominent Th2-polarizing capacity, compared with donor-matched cDCs. Furthermore, such fDCs had tolerogenic properties as judged by higher expression of indolamine dioxigenase-3, IDO-1 and IL-1β and induction of a higher percentage of CD4(+)CD25(+)FoxP3(+) T cells. These findings correlated with increased transforming growth factor (TGF)-β production by fDC-primed CD3(+)T cells and their stronger anti-proliferative capacity. CONCLUSIONS: We emphasize that although fDCs could probably be applied as an alternative to cDCs for cancer therapy, the fDC protocol should not be applied to donors whose DCs acquire tolerogenic capabilities.
BACKGROUND AIMS: Because of the labor-intensive and time-consuming conventional protocols for the generation of dendritic cells (DCs) as the most promising tools for anti-cancer therapy that enable the induction of a T-helper (Th)1-mediated anti-tumor immune response, the use of short-term protocols has been proposed. However, data on the applicability of such protocols in cancer immunotherapy are quite limited. METHODS: We compared the phenotypic and functional capability of fast DCs (fDCs) differentiated for 24 h and then matured for 48 h with Poly (I:C), a strong Th1-promoting agent, with donor-matched conventional DCs (cDCs) differentiated for 5 days and matured likewise. RESULTS: Of 12 donors tested, we identified seven whose monocytes failed to develop into immunogenic DCs through the use of fDC protocol, on the basis of incomplete downregulation of CD14, low expression of CD1a and macrophage-like morphology. Such fDCs have significantly lower expression of CD83, CD86, CCR7 and CD40, weaker allo-stimulatory Th1- and Th17-polarizing capacity caused by poor production of interleukin (IL)-12p70 and IL-23 and high production of IL-10, and prominent Th2-polarizing capacity, compared with donor-matched cDCs. Furthermore, such fDCs had tolerogenic properties as judged by higher expression of indolamine dioxigenase-3, IDO-1 and IL-1β and induction of a higher percentage of CD4(+)CD25(+)FoxP3(+) T cells. These findings correlated with increased transforming growth factor (TGF)-β production by fDC-primed CD3(+)T cells and their stronger anti-proliferative capacity. CONCLUSIONS: We emphasize that although fDCs could probably be applied as an alternative to cDCs for cancer therapy, the fDC protocol should not be applied to donors whose DCs acquire tolerogenic capabilities.
Authors: Dušan Radojević; Sergej Tomić; Dušan Mihajlović; Maja Tolinački; Bojan Pavlović; Dragana Vučević; Svetlana Bojić; Nataša Golić; Miodrag Čolić; Jelena Đokić Journal: Gut Microbes Date: 2021 Jan-Dec