{"id":112234,"date":"2018-03-11T10:39:04","date_gmt":"2018-03-11T10:39:04","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/expression-and-function-of-cd137-4-1bb-in-the-hypoxic-tumor-microenvironment\/"},"modified":"2018-03-11T10:39:04","modified_gmt":"2018-03-11T10:39:04","slug":"expression-and-function-of-cd137-4-1bb-in-the-hypoxic-tumor-microenvironment","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/oncologia\/expression-and-function-of-cd137-4-1bb-in-the-hypoxic-tumor-microenvironment\/","title":{"rendered":"Expression and function of cd137 (4-1bb) in the hypoxic tumor microenvironment"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Francisco De As\u00eds Palaz\u00f3n Garc\u00eda <\/strong><\/h2>\n<p>Los anticuerpos agonistas del receptor de coest\u00edmulo cd137 (4-1bb) est\u00e1n siendo actualmente testados en ensayos cl\u00ednicos para el tratamiento del c\u00e1ncer, por su capacidad de activar la respuesta inmune adaptativa frente al tumor. En este trabajo se ha identificado la expresi\u00f3n selectiva de cd137 en c\u00e9lulas endoteliales que conforman los vasos sangu\u00edneos que irrigan el tumor. La hip\u00f3xia en el microambiente tumoral induce la expresi\u00f3n de cd137 en este tipo celular. Los anticuerpos agonistas de cd137 estimulan a las c\u00e9lulas endoteliales induciendo la expresi\u00f3n de importantes receptores de adhesi\u00f3n (icam-1, vcam-1, e-selectin). Dicha inducci\u00f3n resulta en un aumento del reclutamiento de linfocitos t al tumor, definiendo un mecanismo de acci\u00f3n adicional en la eficacia antitumoral de los anticuerpos agonistas de cd137. La hip\u00f3xia en el microambiente de tumores s\u00f3lidos tambi\u00e9n induce la expresi\u00f3n de cd137 linfocitos t cd4 y cd8 infiltrantes de tumor, concretamente en modelos transplantables de rat\u00f3n de carcinoma de colon, melanoma y un modelo espont\u00e1neo de adenocarcinoma de mama. La expresi\u00f3n de cd137 en linfocitos t es inducida por hip\u00f3xia y por un inhibidor de prolil-hidroxilasas (dmog) que es capaz de estabilizar el principal mediador transcripcional de la respuesta a hip\u00f3xia (hif-1alfa) en condiciones de normoxia (21% o2). De manera importante, la hip\u00f3xia no induce cd137 en linfocitos t infiltrantes de tumor que son deficientes de hif-1alfa, en contraste con la alta expresi\u00f3n de cd137 en linfocitos co-infiltrantes de tumor suficientes para hif-1alfa. El hecho de que cd137 es expresado selectivamente por linfocitos infiltrantes de tumor, frente a los linfocitos presentes en \u00f3rganos linfoides secundarios que expresan bajos niveles de cd137, puede ser explotado con fines terap\u00e9uticos. Para ello se administraron bajas dosis de anticuerpos agonistas de cd137 por v\u00eda intratumoral, evitando los efectos secundarios asociados a la administraci\u00f3n sist\u00e9mica del tratamiento (principalmente inflamaci\u00f3n hep\u00e1tica). En combinaci\u00f3n con anticuerpos bloqueantes del eje inmunoregulador pd-1\/pd-l1(b7h1), este tratamiento obtuvo una alta eficacia antitumoral en un modelo de rat\u00f3n de carcinoma de col\u00f3n transplantable.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Expression and function of cd137 (4-1bb) in the hypoxic tumor microenvironment<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Expression and function of cd137 (4-1bb) in the hypoxic tumor microenvironment <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Francisco De As\u00eds Palaz\u00f3n Garc\u00eda <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 20\/01\/2012<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Ignacio Javier Melero Bermejo<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: manuel Ort\u00edz de land\u00e1zuri busca <\/li>\n<li>Ana Rouzaut subira (vocal)<\/li>\n<li>Juli\u00e1n Aragones lopez (vocal)<\/li>\n<li>randall s. Johnson (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Francisco De As\u00eds Palaz\u00f3n Garc\u00eda Los anticuerpos agonistas del receptor de coest\u00edmulo cd137 (4-1bb) est\u00e1n siendo actualmente [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[1737,17749,1027],"tags":[98255,223368,15058,126721,4670,223369],"class_list":["post-112234","post","type-post","status-publish","format-standard","hentry","category-inmunologia","category-navarra","category-oncologia","tag-ana-rouzaut-subira","tag-francisco-de-asis-palazon-garcia","tag-ignacio-javier-melero-bermejo","tag-julian-aragones-lopez","tag-manuel-ortiz-de-landazuri-busca","tag-randall-s-johnson"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/112234","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=112234"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/112234\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=112234"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=112234"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=112234"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}