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Dexamethasone turns tumor antigen-presenting cells into tolerogenic dendritic cells with T cell inhibitory functions.
Falcón-Beas, Cristián; Tittarelli, Andrés; Mora-Bau, Gabriela; Tempio, Fabián; Pérez, Claudio; Hevia, Daniel; Behrens, Carolina; Flores, Iván; Falcón-Beas, Felipe; Garrido, Paola; Ascui, Gabriel; Pereda, Cristián; González, Fermín E; Salazar-Onfray, Flavio; López, Mercedes N.
Afiliação
  • Falcón-Beas C; 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.
  • Tittarelli A; 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.
  • Mora-Bau G; 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.
  • Tempio F; 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.
  • Pérez C; 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.
  • Hevia D; 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.
  • Behrens C; 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.
  • Flores I; 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.
  • Falcón-Beas F; 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.
  • Garrido P; 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.
  • Ascui G; 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.
  • Pereda C; 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.
  • González FE; 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.
  • Salazar-Onfray F; 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.
  • López MN; 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 Servic
Immunobiology ; 224(5): 697-705, 2019 09.
Article em En | MEDLINE | ID: mdl-31221438
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-1ß and IL-12) and increased release of regulatory cytokines (IL-10 and TGF-ß). Dexamethasone-treated TRIMEL/DCs inhibited allogeneic CD4+ T cell proliferation and cytokine release (IFNγ, TNF-α 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Dendríticas / Dexametasona / Linfócitos T / Tolerância Imunológica / Células Apresentadoras de Antígenos / Antígenos de Neoplasias Limite: Animals / Humans Idioma: En Revista: Immunobiology Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Chile País de publicação: Holanda
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Dendríticas / Dexametasona / Linfócitos T / Tolerância Imunológica / Células Apresentadoras de Antígenos / Antígenos de Neoplasias Limite: Animals / Humans Idioma: En Revista: Immunobiology Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Chile País de publicação: Holanda