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Las citoquinas de células T-helper-1 impulsan el cáncer hacia la senescencia
Heidi Braumüller1, Thomas Wieder, Ellen Brenner
1Department of Dermatology, Eberhard Karls University, Liebermeister Strasse 25, 72076 Tübingen, Germany.
Nature
|February 5, 2013
Resumen
La inmunidad tumoral puede detener el crecimiento del cáncer a través de las células T y el interferón gamma (IFN-γ). La combinación de IFN-γ y el factor de necrosis tumoral (TNF) induce la detención permanente del crecimiento de las células cancerosas, un proceso llamado senescencia.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología del cáncer Biología del cáncer.
- Biología celular Biología celular.
Sus antecedentes:
- La inmunidad adaptativa emplea mecanismos de muerte y limpieza para el control del cáncer.
- La inhibición eficiente del crecimiento del cáncer por las células T y el interferón-γ (IFN-γ) requiere mecanismos adicionales no definidos para detener la proliferación.
Objetivo del estudio:
- Investigar el papel de las citoquinas de células T-helper-1, específicamente IFN-γ y el factor de necrosis tumoral (TNF), en la inducción de la detención permanente del crecimiento del cáncer.
- Para dilucidar los mecanismos moleculares subyacentes a la senescencia inducida por citoquinas en el cáncer.
Principales métodos:
- Utilizó un modelo de ratón que expresaba el antígeno T grande (Tag) del virus Simian 40 para crear tumores con vías p53 y Rb atenuadas.
- La administración combinada de IFN-γ y TNF a cánceres que expresan etiquetas.
- Se evaluó la detención del ciclo celular (G1/G0), la activación de p16INK4a, la hipofosforilación de Rb y la señalización de STAT1 y TNFR1.
- Investigó el papel in vivo de las células T-helper 1 y la señalización de TNFR1 en los cánceres que expresan etiquetas.
Principales resultados:
- La combinación de IFN-γ y TNF induce la detención permanente del crecimiento G1/G0 en los cánceres que expresan Tag, activando p16INK4a y llevando a la hipofosforilación de Rb.
- Esta senescencia inducida por citoquinas requiere la señalización STAT1 y TNFR1.
- In vivo, las células T-helper 1 inducen la senescencia dependiente de IFN-γ y TNFR1, deteniendo permanentemente los cánceres que expresan la etiqueta.
- Los cánceres que carecen de TNFR1 resisten la senescencia inducida por citoquinas y exhiben un crecimiento agresivo.
Conclusiones:
- La acción combinada de IFN-γ y TNF induce directamente la detención permanente del crecimiento (senescencia) en los cánceres.
- Esta senescencia inducida por citoquinas es un mecanismo general para detener la progresión del cáncer, que requiere la señalización STAT1 y TNFR1.
- Dirigirse a estas vías podría ofrecer nuevas estrategias para el control del cáncer.
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