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Partición de nutrientes programada por las células en el microambiente tumoral

Bradley I Reinfeld1,2,3, Matthew Z Madden1,4, Melissa M Wolf2,3

  • 1Medical Scientist Training Program, Vanderbilt University, Nashville, TN, USA.

Nature
|April 8, 2021
PubMed
Resumen
Este resumen es generado por máquina.

Las células inmunes y las células cancerosas consumen preferentemente diferentes nutrientes en el microambiente tumoral (TME). Esta partición de nutrientes intrínseca de la célula, impulsada por la señalización mTORC1, afecta la inmunidad contra el cáncer y podría ser un objetivo para las terapias.

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Área de la Ciencia:

  • Biología del cáncer
  • Inmunología
  • El metabolismo

Sus antecedentes:

  • Las células cancerosas utilizan la glucosa a través del metabolismo de Warburg, formando la base para la tomografía por emisión de positrones (PET).
  • Las células inmunes que se infiltran en el tumor también dependen de la glucosa, y su metabolismo alterado en el microambiente tumoral (TME) puede conducir a la evasión inmune.
  • No está claro si la desregulación metabólica de las células inmunes en el TME se debe a programas intrínsecos o a la competencia de nutrientes con las células cancerosas.

Objetivo del estudio:

  • Investigar la absorción diferencial y la partición de glucosa y glutamina por subconjuntos celulares específicos dentro de la EMT.
  • Para determinar si los programas intrínsecos de la célula o la disponibilidad de nutrientes dictan esta desregulación metabólica.
  • Explorar el potencial terapéutico y de imágenes de la adquisición selectiva de nutrientes en la EMT.

Principales métodos:

  • Se utilizaron marcadores de tomografía por emisión de positrones (PET) para cuantificar la absorción de glucosa y glutamina en poblaciones celulares específicas dentro de la EMT.
  • Analizó la partición de nutrientes en varios modelos de cáncer, incluidas las células mieloides, las células T y las células cancerosas.
  • Se investigó el papel de la diana mecanicista del complejo de rapamicina 1 (mTORC1) y la expresión génica en el metabolismo celular intrínseco de los nutrientes.

Principales resultados:

  • Las células mieloides exhibieron la mayor absorción de glucosa en la EMT, seguidas por las células T y luego por las células cancerosas.
  • Las células cancerosas demostraron la mayor absorción de glutamina en comparación con las células inmunes.
  • Los programas celulares intrínsecos, regulados por la señalización mTORC1, regulan la absorción preferencial de glucosa y glutamina por las células inmunes y cancerosas, respectivamente.
  • La inhibición de la absorción de glutamina aumenta la absorción de glucosa, lo que indica que el metabolismo de la glutamina suprime la utilización de la glucosa independientemente de la limitación de la misma.

Conclusiones:

  • Los programas intrínsecos de la célula dictan la partición distinta de glucosa y glutamina entre las células inmunes y las células cancerosas dentro de la EMT.
  • Esta adquisición selectiva de nutrientes influye en la función de las células inmunes y la progresión del cáncer.
  • Dirigirse a estas vías metabólicas selectivas de las células ofrece potencial para nuevas terapias contra el cáncer y estrategias de imagen avanzadas.