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La señalización de LILRB4 en las células leucémicas media la supresión de las células T y la infiltración tumoral
Mi Deng1, Xun Gui2, Jaehyup Kim3
1Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature
|October 19, 2018
Resumen
La leucemia evade la terapia inmune utilizando LILRB4, un receptor que ayuda a la propagación del tumor y suprime las células T. El bloqueo de LILRB4 es prometedor para el tratamiento de la leucemia mieloide aguda monocítica (LMA).
Área de la Ciencia:
- Inmunología
- En el campo de la oncología
- Biología molecular
Sus antecedentes:
- La terapia de bloqueo de punto de control inmune es efectiva para algunos cánceres, pero no para la leucemia.
- La leucemia puede poseer mecanismos de evasión inmunológica únicos.
- Los receptores inhibidores inmunes en las células leucémicas podrían iniciar la señalización promotora de tumores.
Objetivo del estudio:
- Para investigar el papel de LILRB4 en la leucemia monocítica.
- Para aclarar la vía de señalización por la cual LILRB4 influye en la progresión de la leucemia y la supresión inmune.
Principales métodos:
- Utilizó modelos de ratón y células de leucemia humanas.
- Analizó la vía de señalización LILRB4 que involucra APOE, SHP-2, uPAR y ARG1.
- Se evaluó el impacto de la deleción de LILRB4 y el bloqueo de anticuerpos en el desarrollo de la leucemia.
Principales resultados:
- LILRB4 apoya la infiltración de células tumorales y suprime la actividad de las células T en la leucemia mieloide aguda (LMA).
- La vía LILRB4 (APOE, LILRB4, SHP-2, uPAR, ARG1) es crucial para estos efectos.
- La eliminación o bloqueo de LILRB4 impidió significativamente el desarrollo de LMA en los modelos.
Conclusiones:
- LILRB4 orquesta la invasión tumoral y la supresión inmune en la leucemia monocítica.
- LILRB4 crea un microambiente inmunosupresor, lo que facilita la progresión de la leucemia.
- LILRB4 es un objetivo terapéutico potencial para el tratamiento de la LMA monocítica.
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