Interferon beta increases NK cell cytotoxicity against tumor cells in patients with nasopharyngeal carcinoma via tumor necrosis factor apoptosis-inducing ligand.
Cancer Immunol Immunother
; 68(8): 1317-1329, 2019 Aug.
Article
em En
| MEDLINE
| ID: mdl-31312900
ABSTRACT
BACKGROUND:
Nasopharyngeal carcinoma (NPC) is an EBV-associated neoplasm occurring endemically in Southeast Asia and sporadically all over the world. In children and adolescents, high cure rates have been obtained using chemotherapy, radiochemotherapy and maintenance therapy with interferon beta (IFNß). The mechanism by which IFNß contributes to a low systemic relapse rate has not yet been fully revealed. PATIENTS ANDMETHODS:
NK cells and serum samples from two patients with NPC were analyzed before and at different time points during IFNß therapy, for assessment of TRAIL expression and NK cell cytotoxicity. Cytotoxicity was measured using the calcein release assay and the contribution of different death effector pathways was analyzed using specific inhibitors.RESULTS:
Treatment with IFNß induced TRAIL expression on patients' NK cells and increased their cytotoxicity against NPC targets in vitro. NK cell-mediated cytotoxicity was predominately mediated via TRAIL. IFNß also induced the production of soluble TRAIL (sTRAIL) by NK cells and its release upon contact with NPC cells. IFNß treatment increased serum levels of sTRAIL in patients. Moreover, sTRAIL concentrated from patients' serum samples induced apoptosis ex vivo in NPC cells from a patient-derived xenograft.CONCLUSION:
Increased cytotoxicity of NK cells against NPC cells and increased serum levels of biologically active TRAIL in patients treated with IFNß could be a means to eliminate micrometastatic disease and explain the low systemic relapse rate in this patient group.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
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Interferon beta
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Herpesvirus Humano 4
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Infecções por Vírus Epstein-Barr
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Ligante Indutor de Apoptose Relacionado a TNF
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Carcinoma Nasofaríngeo
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Imunoterapia
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Animals
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Child
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Female
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article