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Identificación de antígenos para los receptores de células T huérfanas expresados en los linfocitos que se infiltran

Marvin H Gee¹, Arnold Han², Shane M Lofgren³

¹Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.

|December 26, 2017

Resumen

La identificación de antígenos tumorales es crucial para la inmunoterapia del cáncer. Este estudio revela que los receptores de células T en los linfocitos que se infiltran en el tumor se pueden examinar para encontrar sus objetivos específicos, incluidos los autoantígenos, ayudando en el descubrimiento del antígeno del cáncer.

Área de la Ciencia:

Inmunología
En el campo de la oncología
Biología molecular

Sus antecedentes:

Los linfocitos que se infiltran en el tumor (TIL) juegan un papel en la inmunidad antitumoral.
Los antígenos específicos reconocidos por las TIL a menudo son desconocidos.
Comprender la especificidad del antígeno TIL es clave para el desarrollo de inmunoterapias contra el cáncer.

Objetivo del estudio:

Identificar las especificidades del antígeno de los receptores de células T (TCR) de las TIL de cáncer colorrectal humano.
Explorar el uso de bibliotecas de péptidos de muestra de levadura para el cribado de TCR.
Para descubrir nuevos antígenos tumorales reconocidos por las TIL.

Principales métodos:

Se utilizaron bibliotecas de muestra de levadura del antígeno peptídico de leucocitos humanos (pHLA) para el cribado.
Detección de antígenos reconocidos por los TCR de las TIL de adenocarcinoma colorrectal.
Se analizó la selección de TCR dentro de una biblioteca de pHLA-A*02:01 diversa.

Principales resultados:

Cuatro TCR derivados de TIL mostraron una fuerte selección en la biblioteca de pHLA.
Tres TCRs reconocieron autoantígenos no mutados.
Dos TCRs reconocieron el mismo autoantígeno derivado de U2AF2, encontrado en diferentes tumores.
Se demostró que los TCR exhiben una alta especificidad para sus antígenos afines.

Conclusiones:

La información estructural sobre los péptidos ligados al MHC es suficiente para identificar los objetivos de la TCR.
Este enfoque de cribado imparcial facilita la identificación de antígenos tumorales.
Los hallazgos apoyan el potencial para apuntar a los autoantígenos reconocidos por las TIL en la terapia del cáncer.

Palabras clave:

Célula T Receptor de las células T Los antígenos el cáncer Biología combinatoria antígeno leucocitario humano Identificación del ligando biblioteca de péptidos Peptídeos y sus derivados secuenciación de una sola célula

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