{"id":90942,"date":"2024-07-19T19:14:59","date_gmt":"2024-07-19T19:14:59","guid":{"rendered":"https:\/\/msdconecta.co.cr\/es\/?post_type=therapeutic-area&p=90942"},"modified":"2024-10-18T22:34:45","modified_gmt":"2024-10-18T22:34:45","slug":"expresion-de-pd-l1-wp-0663","status":"publish","type":"therapeutic-area","link":"https:\/\/msdconecta.co.cr\/es\/therapeutic-areas\/oncologia-wp-0641\/expresion-de-pd-l1-wp-0663\/","title":{"rendered":"Expresi\u00f3n de PD-L1"},"content":{"rendered":"
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\n \"Expresi\u00f3n\n <\/figure>\n\n<\/div>\n\n <\/div>\n\n <\/div>\n\n\n
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Expresi\u00f3n de PD-L1:<\/strong><\/p>\n\n\n\n

Importancia en la predicci\u00f3n de la respuesta a la inmunoterapia<\/strong><\/p>\n\n<\/div>\n\n <\/div>\n\n <\/div>\n\n\n

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La v\u00eda PD-1\/PD-L1<\/mark><\/strong> es usada por una gran variedad de c\u00e9lulas malignas para evadir la vigilancia inmunol\u00f3gica y facilitar el crecimiento tumoral.1<\/sup> La expresi\u00f3n elevada de PD-L1 en las c\u00e9lulas tumorales o los linfocitos que infiltran el tumor causa agotamiento de las c\u00e9lulas T, es decir p\u00e9rdida de su capacidad para eliminar las c\u00e9lulas malignas, lo que conduce a p\u00e9rdida de la inmunidad espec\u00edfica contra el tumor y promueve la progresi\u00f3n tumoral.2<\/sup><\/p>\n\n\n\n

Los inhibidores de la v\u00eda PD-1\/PD-L1<\/mark> <\/strong>promueven la actividad inmunol\u00f3gica antitumoral y su uso ha cambiado el panorama terap\u00e9utico en muchos tipos de c\u00e1ncer, como el melanoma y el c\u00e1ncer pulmonar, renal o mamario, entre otros.3<\/sup> Sin embargo, no todos los pacientes con estos tipos de c\u00e1ncer se benefician de la inmunoterapia, por lo que es esencial disponer de un m\u00e9todo para identificar a los pacientes con mayor probabilidad de beneficiarse del tratamiento.3<\/sup><\/p>\n\n<\/div>\n\n <\/div>\n\n <\/div>\n\n\n\n

<\/div>\n\n\n\n

PD-L1 como marcador predictivo<\/strong><\/p>\n\n\n

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\n \"Expresio\u0301n\n <\/figure>\n\n<\/div>\n\n\n
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PD-L1 es un biomarcador predictivo de la respuesta a los anticuerpos anti PD-1 o anti PD-L1 en pacientes con diversos tipos de c\u00e1ncer.3<\/sup> La expresi\u00f3n de PD-L1 puede detectarse mediante pruebas de inmunohistoqu\u00edmica (IHQ) en las c\u00e9lulas tumorales y en las c\u00e9lulas inmunes que infiltran el tumor, incluyendo macr\u00f3fagos, c\u00e9lulas dendr\u00edticas, neutr\u00f3filos, c\u00e9lulas B y c\u00e9lulas T.3<\/sup><\/p>\n\n<\/div>\n\n <\/div>\n\n <\/div>\n\n\n\n

<\/div>\n\n\n\n

Se dispone de varias pruebas dise\u00f1adas para la expresi\u00f3n de PD-L1, cada una de las cuales se usa en conjunci\u00f3n con un agente terap\u00e9utico particular.3<\/sup> Por ejemplo, la prueba 22C3 est\u00e1 aprobada para medir la expresi\u00f3n de PD-L1 en muestras de c\u00e1ncer pulmonar no microc\u00edtico, c\u00e1ncer de cuello uterino, carcinoma escamocelular de cabeza y cuello, carcinoma escamocelular esof\u00e1gico, c\u00e1ncer mamario triplemente negativo y adenocarcinoma g\u00e1strico o de la uni\u00f3n gastroesof\u00e1gica en pacientes que van a ser tratados con pembrolizumab.4<\/sup> Esta prueba proporciona informaci\u00f3n esencial para el uso seguro y efectivo de pembrolizumab y ayuda al m\u00e9dico a determinar la probabilidad de que el beneficio del tratamiento sea superior a los riesgos en un paciente espec\u00edfico.3<\/sup> De hecho, algunas de las indicaciones de pembrolizumab requieren una evaluaci\u00f3n previa de la expresi\u00f3n de PD-L1 en muestras del tumor.5<\/sup><\/p>\n\n\n

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M\u00e9todos de cuantificaci\u00f3n<\/strong><\/p>\n\n<\/div>\n\n\n

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Existen varias formas de cuantificar la expresi\u00f3n de PD-L1 en las muestras tumorales evaluadas mediante IHQ. Por ejemplo, la prueba 22C3 puede puntuarse usando el puntaje tumoral proporcional (TPS*) o el puntaje positivo combinado (CPS*), as\u00ed:3<\/sup><\/p>\n\n\n

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TPS =<\/strong><\/p>\n\n<\/div>\n\n\n

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N\u00famero de c\u00e9lulas tumorales te\u00f1idas para PD-L1<\/strong><\/p>\n\n\n\n

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N\u00famero total de c\u00e9lulas tumorales viables<\/strong><\/p>\n\n<\/div>\n\n\n

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X 100<\/strong><\/p>\n\n<\/div>\n\n\n

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<\/div>\n\n<\/div>\n\n <\/div>\n\n <\/div>\n\n\n
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CPS =<\/strong><\/p>\n\n<\/div>\n\n\n

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N\u00famero de c\u00e9lulas te\u00f1idas para PD-L1<\/strong><\/p>\n\n\n\n

(c\u00e9lulas<\/em> tumorales, linfocitos y macr\u00f3fagos)<\/em><\/p>\n\n\n\n

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N\u00famero total de c\u00e9lulas tumorales viables<\/strong><\/p>\n\n<\/div>\n\n\n

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X 100<\/strong><\/p>\n\n<\/div>\n\n <\/div>\n\n <\/div>\n\n\n\n

Estos m\u00e9todos de cuantificaci\u00f3n son importantes para la interpretaci\u00f3n de los resultados y para su uso en la pr\u00e1ctica cl\u00ednica en funci\u00f3n del tipo de tumor. Por ejemplo, para los pacientes con c\u00e1ncer pulmonar no microc\u00edtico o adenocarcinoma de cabeza y cuello las indicaciones de pembrolizumab se basan en la medici\u00f3n del TPS5<\/sup>, mientras que para los pacientes con carcinoma urotelial las indicaciones se basan en la medici\u00f3n del CPS.5<\/sup><\/p>\n\n\n\n

*Por sus iniciales en ingl\u00e9s<\/p>\n\n<\/div>\n\n <\/div>\n\n <\/div>\n\n\n\n

Consideraciones importantes<\/strong><\/p>\n\n\n

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\n \"Expresio\u0301n\n <\/figure>\n\n<\/div>\n\n\n
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La utilidad predictiva de la expresi\u00f3n de PD-L1 no es absoluta, por lo que algunos pacientes con expresi\u00f3n de PD-L1 pueden no tener respuesta a la inmunoterapia y, por el contrario, algunos pacientes sin expresi\u00f3n de PD-L1 pueden responder a la inmunoterapia.6<\/sup><\/p>\n\n<\/div>\n\n\n

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\n \"Expresio\u0301n\n <\/figure>\n\n<\/div>\n\n\n
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La expresi\u00f3n de PD-L1 se considera positiva independientemente de si la tinci\u00f3n de la membrana celular es incompleta, pero en los adenocarcinomas la tinci\u00f3n limitada al borde luminal se considera negativa.6<\/sup><\/p>\n\n<\/div>\n\n\n

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\n \"Expresio\u0301n\n <\/figure>\n\n<\/div>\n\n\n
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La expresi\u00f3n de PD-L1 es heterog\u00e9nea, dependiendo de variables como el tipo de tumor (primario vs. metast\u00e1sico), la edad de la muestra, el tipo de muestra (grande vs. peque\u00f1a, biopsia quir\u00fargica vs. biopsia con aguja fina, con tratamiento previo vs. sin tratamiento previo).6<\/sup><\/p>\n\n<\/div>\n\n\n

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\n \"Expresio\u0301n\n <\/figure>\n\n<\/div>\n\n\n
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Siempre que sea posible, debe usarse la muestra tumoral m\u00e1s reciente disponible.7<\/sup><\/p>\n\n<\/div>\n\n\n

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\n \"Expresio\u0301n\n <\/figure>\n\n<\/div>\n\n\n
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Para obtener resultados \u00f3ptimos, el tejido debe fijarse en formaldeh\u00eddo neutral amortiguado al 10%.7<\/sup><\/p>\n\n<\/div>\n\n\n

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\n \"Expresio\u0301n\n <\/figure>\n\n<\/div>\n\n\n
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Las muestras almacenadas en parafina deben tener preferiblemente menos de 3 a\u00f1os.7<\/sup><\/p>\n\n<\/div>\n\n\n

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\n \"Expresio\u0301n\n <\/figure>\n\n<\/div>\n\n\n
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No se recomienda usar sitios descalcificados (ej. met\u00e1stasis \u00f3seas) para la evaluaci\u00f3n de la expresi\u00f3n de PD-L1.7<\/sup><\/p>\n\n<\/div>\n\n <\/div>\n\n <\/div>\n\n\n\n

<\/div>\n\n\n\n
<\/div>\n\n\n\n
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\n \n Acceder o inscribirme a Oncologia- Keytruda para ver m\u00e1s informaci\u00f3n<\/span>\n <\/a><\/div>\n\n\n\n

Referencias<\/strong><\/p>\n\n\n\n

    \n
  1. Davis AA, Patel VG. The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Admi- nistration (FDA) approvals of immune checkpoint inhibitors. JImmunotherCancer<\/em>. 2019;7(1):278<\/li>
  2. Yi M, Jiao D, Xu H, Liu Q, Zhao W, Han X, Wu K. Biomarkers for predicting efficacy of PD-1\/PD-L1 inhibitors. MolCancer.<\/em> 2018;17(1):129.<\/li>
  3. Doroshow DB, Bhalla S, Beasley MB, Sholl LM, Kerr KM, Gnjatic S, Wistuba II, Rimm DL, Tsao MS, Hirsch FR. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. NatRevClinOncol.<\/em>2021;18(6):345-362.<\/li>
  4. Food and Drug Administration. List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools). Disponible en: https:\/\/www.fda.gov\/medical-devices\/in-vitro-diagnostics\/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools<\/a>. Consultado el 09 de abril de 2024.<\/li>
  5. Keytruda. Informaci\u00f3n para Prescribir. 2019. MK3475-CENA-2019 020289. Datos en archivo. <\/li>
  6. Vranic S, Gatalica Z. PD-L1 testing by immunohistochemistry in immuno-oncology. BiomolBiomed.<\/em>2023;23(1):15-25. <\/li>
  7. Parischa S, Durga G, Babu V, et al. PD-L1 Testing and Assessment: Practical Considerations for Oncologist and Patholo- gist. IndJMedPaediatrOncol.<\/em>2022;11-28.<\/li><\/ol>\n\n\n\n
    <\/div>\n\n\n\n
    \n","protected":false},"excerpt":{"rendered":"

    PD-L1 como marcador predictivo Se dispone de varias pruebas dise\u00f1adas para la expresi\u00f3n de PD-L1, cada una de las cuales 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