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La remodelación del peptidoglicano por enterococos promueve la inmunoterapia contra el cáncer por inhibidores de los
Matthew E Griffin1,2,3,2,1, Juliel Espinosa1,2, Jessica L Becker1,2
1Departments of Immunology and Microbiology and Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science (New York, N.Y.)
|August 27, 2021
Resumen
Ciertas bacterias intestinales, como Enterococcus, mejoran la inmunoterapia del cáncer al producir moléculas inmunológicas activas. Esto sugiere que se podrían desarrollar enzimas bacterianas y muropéptidos específicos como nuevos adyuvantes para el tratamiento del cáncer.
Área de la Ciencia:
- Microbiología
- Inmunología
- En el campo de la oncología
Sus antecedentes:
- La composición del microbioma intestinal influye en la eficacia de la inmunoterapia contra el cáncer.
- Los mecanismos moleculares que vinculan las bacterias intestinales y la respuesta a la inmunoterapia no se comprenden completamente.
Objetivo del estudio:
- Investigar el papel del género bacteriano *Enterococcus* en la mejora de la inmunoterapia contra el cáncer.
- Identificar los mecanismos moleculares por los que el enterococo influye en la respuesta del huésped a la inmunoterapia.
Principales métodos:
- Se utilizaron modelos de tumores de ratón para evaluar el impacto de *Enterococcus* en la inmunoterapia con inhibidores de punto de control.
- Investigó la expresión y función de la enzima SagA y su papel en la generación de muropéptidos inmunológicamente activos.
- Se examinó la necesidad del sensor NOD2 para la actividad de SagA y la respuesta a la inmunoterapia.
Principales resultados:
- Se encontró que las especies *Enterococcus* mejoran la inmunoterapia con inhibidores de punto de control en modelos de ratón.
- La enzima bacteriana SagA (una hidrolasa de peptidoglicano NlpC/p60) genera muropéptidos inmunológicamente activos.
- La expresión de SagA en *E. faecalis* mejora la respuesta a la inmunoterapia, dependiendo del sensor NOD2.
- Los probióticos diseñados y los muropéptidos sintéticos que contienen actividad SagA aumentaron la eficacia anti-PD-L1.
Conclusiones:
- La actividad de remodelación del peptidoglicano bacteriano, mediada por enzimas como SagA, mejora la inmunoterapia contra el cáncer.
- Los muropéptidos inmunológicamente activos producidos por bacterias pueden servir como adyuvantes para mejorar los resultados de la inmunoterapia.
- Dirigirse a las enzimas bacterianas y a los muropéptidos presenta una estrategia potencial para las terapias contra el cáncer de próxima generación.
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