PMID- 31221438 OWN - NLM STAT- MEDLINE DCOM- 20200226 LR - 20200226 IS - 1878-3279 (Electronic) IS - 0171-2985 (Linking) VI - 224 IP - 5 DP - 2019 Sep TI - Dexamethasone turns tumor antigen-presenting cells into tolerogenic dendritic cells with T cell inhibitory functions. PG - 697-705 LID - S0171-2985(19)30029-4 [pii] LID - 10.1016/j.imbio.2019.05.011 [doi] AB - BACKGROUND: Dendritic cells (DCs) are usually immunogenic, but they are also capable of inducing tolerance under anti-inflammatory conditions. Immunotherapy based on autologous DCs loaded with an allogeneic melanoma cell lysate (TRIMEL/DCs) induces immunological responses and increases melanoma patient survival. Glucocorticoids can suppress DC maturation and function, leading to a DC-mediated inhibition of T cell responses. METHODS: The effect of dexamethasone, a glucocorticoid extensively used in cancer therapies, on TRIMEL/DCs phenotype and immunogenicity was examined. RESULTS: Dexamethasone induced a semi-mature phenotype on TRIMEL/DC with low maturation surface marker expressions, decreased pro-inflammatory cytokine induction (IL-1beta and IL-12) and increased release of regulatory cytokines (IL-10 and TGF-beta). Dexamethasone-treated TRIMEL/DCs inhibited allogeneic CD4(+) T cell proliferation and cytokine release (IFNgamma, TNF-alpha and IL-17). Co-culturing melanoma-specific memory tumor-infiltrating lymphocytes with dexamethasone-treated TRIMEL/DC inhibited proliferation and effector T cell activities, including cytokine secretion and anti-melanoma cytotoxicity. CONCLUSIONS: These findings suggest that dexamethasone repressed melanoma cell lysate-mediated DC maturation, generating a potent tolerogenic-like DC phenotype that inhibited melanoma-specific effector T cell activities. These results suggest that dexamethasone-induced immunosuppression may interfere with the clinical efficacy of DC-based melanoma vaccines, and must be taken into account for optimal design of cellular therapy against cancer. CI - Copyright (c) 2019. Published by Elsevier GmbH. FAU - Falcon-Beas, Cristian AU - Falcon-Beas C AD - Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. FAU - Tittarelli, Andres AU - Tittarelli A AD - Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. FAU - Mora-Bau, Gabriela AU - Mora-Bau G AD - Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. FAU - Tempio, Fabian AU - Tempio F AD - Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. FAU - Perez, Claudio AU - Perez C AD - Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Cell Therapy Laboratory, Blood Bank Service, University of Chile Clinical Hospital, 8380453 Santiago, Chile. FAU - Hevia, Daniel AU - Hevia D AD - Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. FAU - Behrens, Carolina AU - Behrens C AD - Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. FAU - Flores, Ivan AU - Flores I AD - Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. FAU - Falcon-Beas, Felipe AU - Falcon-Beas F AD - Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. FAU - Garrido, Paola AU - Garrido P AD - Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. FAU - Ascui, Gabriel AU - Ascui G AD - Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. FAU - Pereda, Cristian AU - Pereda C AD - Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. FAU - Gonzalez, Fermin E AU - Gonzalez FE AD - Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Laboratory of Experimental Immunology & Cancer, Department of Conservative Dentistry, Faculty of Dentistry, University of Chile, 8380492 Santiago, Chile. FAU - Salazar-Onfray, Flavio AU - Salazar-Onfray F AD - Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. FAU - Lopez, Mercedes N AU - Lopez MN AD - Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Cell Therapy Laboratory, Blood Bank Service, University of Chile Clinical Hospital, 8380453 Santiago, Chile. Electronic address: melopez@me.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190606 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - 0 (Antigens, Neoplasm) RN - 0 (Cytokines) RN - 7S5I7G3JQL (Dexamethasone) SB - IM MH - Animals MH - Antigen-Presenting Cells/*drug effects/*immunology/metabolism MH - Antigens, Neoplasm/*immunology MH - Cytokines/metabolism MH - Dendritic Cells/*immunology/metabolism MH - Dexamethasone/*pharmacology MH - Humans MH - *Immune Tolerance MH - Immunomodulation MH - Immunophenotyping MH - Lymphocyte Activation/immunology MH - Lymphocytes, Tumor-Infiltrating/drug effects/immunology/metabolism MH - Mice MH - Phenotype MH - T-Lymphocyte Subsets/immunology/metabolism MH - T-Lymphocytes/*immunology/metabolism OTO - NOTNLM OT - Dendritic cells OT - Dexamethasone OT - Melanoma OT - Regulatory T cells OT - Tolerance EDAT- 2019/06/22 06:00 MHDA- 2020/02/27 06:00 CRDT- 2019/06/22 06:00 PHST- 2019/01/28 00:00 [received] PHST- 2019/05/05 00:00 [revised] PHST- 2019/05/30 00:00 [accepted] PHST- 2019/06/22 06:00 [pubmed] PHST- 2020/02/27 06:00 [medline] PHST- 2019/06/22 06:00 [entrez] AID - S0171-2985(19)30029-4 [pii] AID - 10.1016/j.imbio.2019.05.011 [doi] PST - ppublish SO - Immunobiology. 2019 Sep;224(5):697-705. doi: 10.1016/j.imbio.2019.05.011. Epub 2019 Jun 6.