Dexamethasone inhibits tumor cell lysate induction of a pro-inflammatory dendritic cell phenotype and function modulating T cell cytokine profiles (P4246)
| Autor: | Cristian Falcon, Fabian Tempio, Claudio Perez, Carolina Behrens, Ana-Adelia Riberos, Felipe Falcon, Flavio Salazar-Onfray, Mercedes Lopez |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 190:47.11-47.11 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.190.supp.47.11 |
| Popis: | Recently, we showed the effectiveness of a DCs-based immunotherapy for improving long-term survival in patients with melanoma using an allogeneic melanoma cell lysate. Glucocorticoids are used in cancer patients being implicated in immune suppression. Here, we aim to study the effect of dexamethasone on the inhibition of the pro-inflammatory phenotype and immunogenicity capacity of melanoma cell lysate-loaded DCs. Monocytes were differentiated to DCs as previously described. Dexamethasone was given at day 1 and 2 to obtain tolerogenic DCs. DCs maturation markers and TH1, TH17 phenotype were determined by flow cytometry. T cell cytokines were measured by ELISA and proliferation evaluated by CFSE dilution assay. We show that dexametasone stimulus elicits a semi-mature DC phenotype (low MHC II, CD83, CD80 and CD86) sharing mature and immature DCs characteristics, secreting low levels of IL1β, IL-6 and IL-12 and high levels of IL-10, but not affecting DC phagocytosis capacity. TolDCs inhibited T cell proliferation and IFNγ, IL-17 and TNF-α release by T helper cells. At contrary, an augment of Treg cells could be observed. The used glucocorticoids affects the maturation of newly differentiated monocytes-derived DCs in presence of immunogenic tumor cells, affecting the activation of a correct adaptive anti tumor immunity. |
| Databáze: | OpenAIRE |
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