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Ministerio de Universidades - Gobierno de España

Título: CELLULAR IMMUNOTHERAPY FOR B-CELL LYMPHOMA WITH NKT-CELL AGONISTS
Autor: Escribà Garcia, Laura
Universidad: Universidad Autónoma de Barcelona
Departamento: Bioquimica i biologia molecular
Fecha de Lectura: 26/05/2016
Programa de doctorado: Programa de Doctorado en Bioquímica, Biología Molecular y Biomedicina por la Universidad Autónoma de Barcelona
Dirección:
- BRIONES MEIJIDE, JAVIER (DIRECTOR)
- Bosch Merino, Assumpció (TUTOR/PONENTE)
Tribunal:
- DOMINGUEZ PUENTE, FERNANDO (PRESIDENTE)
- CHILLON RODRIGUEZ, MIGUEL (SECRETARIO)
- Llebaria Soldevila, Amadeu (VOCAL)
Descriptores:
- BIOLOGIA CELULAR
Localización: BIBLIOTECA DE COMUNICACIÓN Y HEMEROTECA GENERAL UAB
Marcador: https://www.educacion.gob.es/teseo/mostrarRef.do?ref=1263492Añadir a favoritos.
Resumen:
Natural killer T (NKT) cells are a small population of lymphocytes with unique specificity for glycolipid antigens presented by non-polymorphic CD1d receptor on APC, mainly presented on dendritic cells (DCs). NKT cells play a central role in tumor immunology since they coordinate innate and adaptive immune responses. These cells can be activated with the prototypic lipid ¿-galactosylceramide (¿-GalCer), stimulating IFN-¿ production and cytokine secretion (eg, IL-12, IL-4, IL-17) that contribute to the enhancement of DC function and the induction of NK, B and T-cell activation. We evaluated the antitumor effect of a combination of DCs and irradiated tumor cells with the NKT cell agonist ¿-GalCer in a mouse model of B-cell lymphoma. The therapeutic vaccine consisting of DCs, tumor cells and ¿-GalCer was able to eradicate B-cell lymphoma in all treated mice, and was superior to any vaccine combination, including ¿-GalCer alone, irradiated tumor cells with DCs, and DCs with ¿-GalCer. Importantly, treated mice with the vaccine were resistant to a tumor rechallenge, suggesting the development of a memory immune response. In addition, the immune response was tumor-specific since all the mice were unable to reject a syngeneic A20 B-cell lymphoma. In addition to in vivo evaluation of the therapeutic vaccine, the cytokine profile induced by the treatment was evaluated, showing a combination of Th1 and Th2 cytokines together with IL-17. When we looked at effector cells, we observed that the vaccine induces a high NKT and NK-cell expansion, as well as a high increase of IFN-¿ secreting NKT, NK and tumor-specific T cells. NK cells played a critical role in the antitumor effect observed after the therapeutic treatment and there was also an activation of B cells since IgG antibodies against tumor cells were found in treated mice. The therapeutic vaccine consisting of dendritic cells, tumor cells and ¿-GalCer efficiently eradicates B-cell lymphoma in a therapeutic setting. This immune response is long-lasting, tumor-specific, and it is associated with an expansion of NK and NKT cells, an increase of IFN-¿ secreting NK, NKT and T cells and B-cell activation.

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