{"id":41987,"date":"2023-08-11T00:00:02","date_gmt":"2023-08-11T07:00:02","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=41987"},"modified":"2024-01-30T14:12:23","modified_gmt":"2024-01-30T22:12:23","slug":"using-the-bodys-invisible-scalpel-to-remove-brain-cancer","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/using-the-bodys-invisible-scalpel-to-remove-brain-cancer\/","title":{"rendered":"Utilizar el \u201cbistur\u00ed invisible\u201d del cuerpo para extirpar el c\u00e1ncer cerebral"},"content":{"rendered":"

LA JOLLA\u2014El glioblastoma, la forma m\u00e1s com\u00fan y mortal de c\u00e1ncer cerebral, crece r\u00e1pidamente para invadir y destruir el tejido cerebral sano. El tumor env\u00eda zarcillos cancerosos al cerebro que hacen que la extirpaci\u00f3n quir\u00fargica del tumor sea extremadamente dif\u00edcil o imposible.<\/p>\n

Ahora, cient\u00edficos de Salk han descubierto que el tratamiento de inmunoterapia anti-CTLA-4 conduce a una supervivencia considerablemente mayor de ratones con glioblastoma. Adem\u00e1s, descubrieron que esta terapia depend\u00eda de la infiltraci\u00f3n de c\u00e9lulas inmunitarias llamadas c\u00e9lulas T CD4+ en el cerebro y de la activaci\u00f3n de las actividades destructoras del tumor de otras c\u00e9lulas inmunitarias llamadas microgl\u00eda, que residen permanentemente en el cerebro.<\/p>\n

\"From
De izquierda a derecha: Susan Kaech, Dan Chen y Siva Karthik Varanasi. Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.
Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>\n

Publicado en Inmunidad<\/em><\/a> el 11 de agosto de 2023, los hallazgos demuestran el beneficio de aprovechar las propias c\u00e9lulas inmunitarias del cuerpo para combatir el c\u00e1ncer cerebral y podr\u00edan conducir a inmunoterapias m\u00e1s efectivas para tratar el c\u00e1ncer cerebral en humanos.<\/p>\n

\u201cActualmente no existen tratamientos efectivos para el glioblastoma, un diagn\u00f3stico que hoy en d\u00eda es b\u00e1sicamente una sentencia de muerte\u201d, afirma el profesor Susan Kaech<\/a>, autor principal y director del Centro NOMIS para Inmunobiolog\u00eda y Patog\u00e9nesis Microbiana. \u201cEstamos extremadamente emocionados de encontrar un r\u00e9gimen de inmunoterapia que utiliza las propias c\u00e9lulas inmunes del rat\u00f3n para combatir el c\u00e1ncer cerebral y que conduce a una reducci\u00f3n considerable, y en algunos casos eliminaci\u00f3n, del tumor.\u201d<\/p>\n

Cuando los tratamientos est\u00e1ndar contra el c\u00e1ncer como la cirug\u00eda, la quimioterapia y la radioterapia dejan de ser efectivos, los m\u00e9dicos recurren cada vez m\u00e1s a la inmunoterapia. La inmunoterapia estimula a las propias c\u00e9lulas inmunitarias del cuerpo a buscar y destruir las c\u00e9lulas cancerosas. Aunque no es universal, la inmunoterapia funciona en muchos tumores y ha proporcionado a muchos pacientes respuestas anticancerosas fuertes y duraderas. Kaech quiso encontrar nuevas formas de aprovechar el sistema inmunitario para desarrollar tratamientos m\u00e1s seguros y duraderos para el c\u00e1ncer cerebral.<\/p>\n

Su equipo encontr\u00f3 tres herramientas de lucha contra el c\u00e1ncer que han sido algo pasadas por alto en la investigaci\u00f3n del c\u00e1ncer cerebral y que pueden cooperar y atacar eficazmente el glioblastoma: un f\u00e1rmaco inmunoterap\u00e9utico llamado anti-CTLA-4 y dos c\u00e9lulas inmunitarias especializadas llamadas c\u00e9lulas T CD4+ y microgl\u00eda.<\/p>\n

La inmunoterapia anti-CTLA-4 funciona bloqueando la producci\u00f3n de la prote\u00edna CTLA-4, la cual, si no se bloquea, inhibe la actividad de las c\u00e9lulas T. Fue el primer f\u00e1rmaco de inmunoterapia dise\u00f1ado para estimular nuestro sistema inmunol\u00f3gico a luchar contra el c\u00e1ncer, pero pronto fue seguido por otro, el anti-PD-1, que era menos t\u00f3xico y se us\u00f3 m\u00e1s ampliamente. Todav\u00eda se desconoce si el anti-CTLA-4 es un tratamiento eficaz para el glioblastoma, ya que el anti-PD-1 tuvo prioridad en los ensayos cl\u00ednicos. Desafortunadamente, se descubri\u00f3 que el anti-PD-1 era ineficaz en m\u00faltiples ensayos cl\u00ednicos para el glioblastoma, un fracaso que inspir\u00f3 a Kaech a ver si el anti-CTLA-4 ser\u00eda diferente.<\/p>\n

\"Anti-CTLA-4
La terapia anti-CTLA-4 induce la infiltraci\u00f3n de c\u00e9lulas T asesinas del sistema inmunitario (cian) en el glioblastoma (verde) y promueve una asociaci\u00f3n antitumoral con c\u00e9lulas inmunitarias residentes en el cerebro llamadas microgl\u00eda (magenta).
Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.
Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>\n

En cuanto a las c\u00e9lulas inmunitarias especializadas, las c\u00e9lulas T CD4+ a menudo son pasadas por alto en la investigaci\u00f3n del c\u00e1ncer en favor de una c\u00e9lula inmunitaria similar, la c\u00e9lula T CD8+, porque se sabe que las c\u00e9lulas T CD8+ matan directamente las c\u00e9lulas cancerosas. La microglia vive en el cerebro a tiempo completo, donde patrulla en busca de invasores y responde a los da\u00f1os; si desempe\u00f1an alg\u00fan papel en la muerte del tumor no estaba claro.<\/p>\n

Primero, los investigadores compararon la esperanza de vida de ratones con glioblastoma al ser tratados con anti-CTLA-4 versus anti-PD-1. Despu\u00e9s de descubrir que el bloqueo de CTLA-4 prolongaba considerablemente su esperanza de vida, pero el bloqueo de PD-1 no, el equipo pas\u00f3 a determinar qu\u00e9 hac\u00eda posible ese resultado.<\/p>\n

Descubrieron que despu\u00e9s del tratamiento anti-CTLA-4, las c\u00e9lulas T CD4+ secretaban una prote\u00edna llamada interfer\u00f3n gamma que provocaba que el tumor desplegara \u201cbanderas de estr\u00e9s\u201d mientras alertaba simult\u00e1neamente a la microgl\u00eda para que comenzara a devorar esas c\u00e9lulas tumorales estresadas. A medida que engull\u00edan las c\u00e9lulas tumorales, la microgl\u00eda presentaba fragmentos del tumor en su superficie para mantener las c\u00e9lulas T CD4+ atentas y produciendo m\u00e1s interfer\u00f3n gamma, creando un ciclo que se repite hasta que el tumor es destruido.<\/p>\n

\u201cNuestro estudio demuestra la promesa de los anti-CTLA-4 y describe un proceso novedoso en el que las c\u00e9lulas T CD4+ y otras c\u00e9lulas inmunes residentes en el cerebro se unen para eliminar c\u00e9lulas cancerosas\u201d, dice Dan Chen, coautor principal e investigador postdoctoral en el laboratorio de Kaech.<\/p>\n

Para entender el papel de la microglia en este ciclo, los investigadores colaboraron con el coautor y profesor de Salk Greg Lemke<\/a>, titular de la C\u00e1tedra Fran\u00e7oise Gilot-Salk. Durante d\u00e9cadas, Lemke ha investig\u00f3 mol\u00e9culas cr\u00edticas, llamadas receptores TAM, utilizadas por la microgl\u00eda<\/a> para enviar y recibir mensajes cruciales. Los investigadores descubrieron que los receptores TAM le indicaban a la microgl\u00eda que absorbiera las c\u00e9lulas cancerosas en este novedoso ciclo.<\/p>\n

\u201cNos quedamos asombrados por esta novedosa codependencia entre la microgl\u00eda y las c\u00e9lulas T CD4+\u201d, dice el coautor Siva Karthik Varanasi, investigador postdoctoral en el laboratorio de Kaech. \u201cYa estamos entusiasmados con tantas nuevas preguntas biol\u00f3gicas y soluciones terap\u00e9uticas que podr\u00edan cambiar radicalmente el tratamiento de c\u00e1nceres mortales como el glioblastoma\u201d.\u201d<\/p>\n

Conectar las piezas de este rompecabezas que mata el c\u00e1ncer acerca a los investigadores m\u00e1s que nunca a la comprensi\u00f3n y el tratamiento del glioblastoma.<\/p>\n

\u201cAhora podemos reimaginar el tratamiento del glioblastoma intentando convertir la microgl\u00eda local que rodea los tumores cerebrales en destructora de tumores\u201d, afirma Kaech, titular de la C\u00e1tedra NOMIS. \u201cDesarrollar una asociaci\u00f3n entre las c\u00e9lulas T CD4+ y la microgl\u00eda est\u00e1 creando un nuevo tipo de respuesta inmune productiva que no conoc\u00edamos previamente\u201d.\u201d<\/p>\n

A continuaci\u00f3n, los investigadores examinar\u00e1n si este ciclo celular que mata el c\u00e1ncer est\u00e1 presente en casos de glioblastoma en humanos. Adicionalmente, su objetivo es estudiar otros modelos animales con subtipos de glioblastoma diferentes, ampliando su comprensi\u00f3n de la enfermedad y los tratamientos \u00f3ptimos.<\/p>\n

Otros autores incluyen a Toshiro Hara, Kacie Traina, Ming Sun, Bryan McDonald, Yagmur Farsakoglu, Josh Clanton, Shihao Xu, Lizmarie Garcia-Rivera, Thomas H. Mann, Victor Du, H. Kay Chung, Ziyan Xu, Victoria Tripple, Eduardo Casillas, Shixin Ma, Carolyn O\u2019Connor, Qiyuan Yang, Ye Zheng y Tony Hunter de Salk.<\/p>\n

El trabajo fue apoyado por los National Institutes of Health (CA195613), el Cancer Research Institute, la Damon Runyon Cancer Research Foundation y una beca del National Cancer Center.<\/p>","protected":false},"featured_media":42117,"template":"","faculty":[311],"disease-research":[178,46,122],"class_list":["post-41987","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-susan-kaech","disease-research-brain-cancer","disease-research-cancer-biology","disease-research-immune-system-biology"],"acf":[],"yoast_head":"\nUsing the body\u2019s \u201cinvisible scalpel\u201d to remove brain cancer - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/es\/news-release\/using-the-bodys-invisible-scalpel-to-remove-brain-cancer\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Using the body\u2019s \u201cinvisible scalpel\u201d to remove brain cancer - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Glioblastoma, the most common and deadly form of brain cancer, grows rapidly to invade and destroy healthy brain tissue. 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