{"id":5952,"date":"2025-04-22T10:55:51","date_gmt":"2025-04-22T08:55:51","guid":{"rendered":"https:\/\/rvh-synergie.org\/actualites\/limmunogenicite-faible-du-carcinome-basal-lie-a-la-suppression-de-la-presentation-de-lantigene-de-sa-cellule-dorigine\/"},"modified":"2025-04-22T10:55:52","modified_gmt":"2025-04-22T08:55:52","slug":"limmunogenicite-faible-du-carcinome-basal-lie-a-la-suppression-de-la-presentation-de-lantigene-de-sa-cellule-dorigine","status":"publish","type":"post","link":"https:\/\/rvh-synergie.org\/actualites\/limmunogenicite-faible-du-carcinome-basal-lie-a-la-suppression-de-la-presentation-de-lantigene-de-sa-cellule-dorigine\/","title":{"rendered":"L’immunog\u00e9nicit\u00e9 faible du carcinome basal li\u00e9 \u00e0 la suppression de la pr\u00e9sentation de l’antig\u00e8ne de sa cellule d’origine"},"content":{"rendered":"
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La pr\u00e9sentation de l’antig\u00e8ne compromis se classe parmi les principaux m\u00e9canismes qui rendent les cancers non immunog\u00e8nes (non r\u00e9actifs aux th\u00e9rapies \u00e0 base immunitaire). Malgr\u00e9 le port de la charge mutationnelle tumorale la plus \u00e9lev\u00e9e de tous les cancers, les carcinomes basoceliques (BCC) ont une faible immunog\u00e9nicit\u00e9.<\/p>\n

La perte des composants des antig\u00e8nes de leucocytes humains de classe I (HLA-I) est particuli\u00e8rement r\u00e9pandu dans les cancers immunitaires.<\/p>\n

Les antig\u00e8nes tumoraux sont captur\u00e9s et affich\u00e9s par le traitement des antig\u00e8nes et les machines de pr\u00e9sentation (APM) sur la surface des cellules par HLA-I, ce qui le permet de CD8+<\/sup> Les cellules T pour \u00e9liminer les cellules canc\u00e9reuses. Cependant, les cellules canc\u00e9reuses ont d\u00e9velopp\u00e9 divers moyens pour limiter l’APM et \u00e9chapper \u00e0 la reconnaissance immunitaire.<\/p>\n

Shawn Demehri, MD, Ph.D., m\u00e9decin-investigateur au Cutaneous Biology Research Center et Krantz Family Center for Cancer Research au Massachusetts General Hospital et professeur agr\u00e9g\u00e9 de dermatologie \u00e0 la Harvard Medical School, est l’auteur principal d’une \u00e9tude en Rapports cellulaires<\/i>intitul\u00e9 \u00ab\u00a0La r\u00e9gulation \u00e9pig\u00e9nomique de la tige contribue \u00e0 la faible immunog\u00e9nicit\u00e9 du cancer humain le plus mut\u00e9.\u00a0\u00bb<\/p>\n

Pour d\u00e9terminer l’\u00e9tat immunitaire de BCC, l’\u00e9quipe de recherche de Demehri a \u00e9tudi\u00e9 une grande collection de BCC humains primaires par rapport aux carcinomes \u00e9pidermo\u00efdes (SCC), qui se sont r\u00e9v\u00e9l\u00e9s plus sensibles aux th\u00e9rapies \u00e0 base immunitaire. Ils ont d\u00e9couvert que les BCC primaires avaient un ph\u00e9notype immunitaire-exclu associ\u00e9 \u00e0 une expression minimale de HLA-I par les cellules canc\u00e9reuses, m\u00eame pendant leur d\u00e9veloppement pr\u00e9coce.<\/p>\n

Les chercheurs ont \u00e9galement d\u00e9termin\u00e9 qu’un programme de repos de type STEM qui a persist\u00e9 \u00e0 partir de la cellule d’origine de la tumeur a supprim\u00e9 les g\u00e8nes APM dans les cellules BCC, et que l’inversion \u00e9pig\u00e9nomique de la suppression du g\u00e8ne APM a permis l’immunoth\u00e9rapie BCC.<\/p>\n

Ces r\u00e9sultats r\u00e9v\u00e8lent la cellule d’origine comme le d\u00e9terminant dominant de l’immunog\u00e9nicit\u00e9 du cancer dans les BCC et indiquent une nouvelle approche qui pourrait am\u00e9liorer le traitement.<\/p>\n

Le carcinome k\u00e9ratinocytaire, y compris les BCC et les SCC cutan\u00e9s, est le cancer le plus courant avec une augmentation continue de l’incidence.<\/p>\n

Les SCC pr\u00e9sentent un taux de r\u00e9ponse objectif de 49,3% \u00e0 la th\u00e9rapie PD-1, tandis que le BCC m\u00e9tastatique n’a que 21% de th\u00e9rapie anti-PD-1.<\/p>\n

Les transplant\u00e9s d’organes sur les immunosuppresseurs syst\u00e9miques pr\u00e9sentent un risque de SCC plus \u00e9lev\u00e9 \u00e0 plus de 100 fois plus \u00e9lev\u00e9 par rapport \u00e0 la population g\u00e9n\u00e9rale, mais seulement un risque de BCC de six \u00e0 16 fois plus \u00e9lev\u00e9, ce qui sugg\u00e8re que le BCC peut manquer d’immunog\u00e9nicit\u00e9.<\/p>\n

Demehri explique: \u00ab\u00a0Pour d\u00e9terminer l’\u00e9tat immunitaire de BCC, nous avons \u00e9tudi\u00e9 une grande collection de BCC humains primaires par rapport aux SCC. Bien que les cellules T aient \u00e9t\u00e9 d\u00e9tectables dans le stroma entourant le BCC, significativement moins CD4 CD4+<\/sup> et CD8+<\/sup> Les cellules T infiltr\u00e9es dans les foyers de tumeurs BCC par rapport aux SCC. Une \u00e9tude des autres cellules immunitaires a r\u00e9v\u00e9l\u00e9 qu’elles \u00e9taient \u00e9galement significativement r\u00e9duites dans le BCC par rapport au SCC.<\/p>\n

\u00ab\u00a0Le s\u00e9quen\u00e7age d’ARN unique sur des \u00e9chantillons BCC et SCC recueillis avec des m\u00e9thodes de pr\u00e9paration de cellules similaires a montr\u00e9 des populations de cellules immunitaires beaucoup plus petites dans le BCC par rapport au SCC.<\/p>\n

\u00ab\u00a0Surtout, les premiers BCC avec des cellules T rares dans le stroma ont montr\u00e9 une faible expression HLA-I, indiquant que de faibles niveaux d’APM dans le BCC proviennent d’un m\u00e9canisme intrins\u00e8que int\u00e9gral \u00e0 sa biologie du d\u00e9veloppement.<\/p>\n

\u00ab\u00a0Nous avons \u00e9galement constat\u00e9 que FOXC1 est un suppresseur critique de IRF1 et HLA-I dans les cellules BCC, rappelant sa fonction dans les cellules souches du follicule pileux quiescente. FOXC1 r\u00e9gule \u00e0 la baisse IRF1 et HLA-I par des m\u00e9canismes \u00e9pig\u00e9nomiques, qui peuvent \u00eatre r\u00e9vers\u00e9s pour permettre l’immunoth\u00e9rapie BCC.\u00a0\u00bb<\/p>\n

Implications cliniques<\/h2>\n

\u00ab\u00a0Nous d\u00e9montrons que le traitement topique de l’entinostat r\u00e9gule \u00e0 la hausse la pr\u00e9sentation de l’antig\u00e8ne dans le BCC in vivo\u00a0\u00bb, poursuit Demehri. \u00abEn tant que tel, la combinaison de l’entinostat avec l’immunoth\u00e9rapie topique et syst\u00e9mique est la cl\u00e9 pour permettre l’immunoth\u00e9rapie BCC.<\/p>\n

\u00ab\u00a0Pour y parvenir, nous avons combin\u00e9 l’entinostat topique avec une immunoth\u00e9rapie topique approuv\u00e9e par la FDA, l’imiquimod. La haute efficacit\u00e9 de l’imiquimod entinostat plus dans la suppression du d\u00e9veloppement du BCC indique que l’imiquimod induit par l’entinostat dans le BCC dans le BCC.<\/p>\n

\u00ab\u00a0Sur la base de nos r\u00e9sultats, un premier essai clinique humain est justifi\u00e9 pour \u00e9tudier l’efficacit\u00e9 de cette th\u00e9rapie combin\u00e9e pour le traitement du BCC chez l’homme.\u00a0\u00bb<\/p>\n

<\/p><\/div>\n","protected":false},"excerpt":{"rendered":"

La pr\u00e9sentation de l’antig\u00e8ne compromis se classe parmi les principaux m\u00e9canismes qui rendent les cancers<\/p>\n","protected":false},"author":1,"featured_media":5953,"comment_status":"closed","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[86],"tags":[5001,5000,5004,857,425,5003,954,4999,5002,4147],"class_list":["post-5952","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-les-maladies","tag-basal","tag-carcinome","tag-cellule","tag-dorigine","tag-faible","tag-lantigene","tag-lie","tag-limmunogenicite","tag-presentation","tag-suppression","generate-columns","tablet-grid-50","mobile-grid-100","grid-parent","grid-50","resize-featured-image"],"yoast_head":"\nL'immunog\u00e9nicit\u00e9 faible du carcinome basal li\u00e9 \u00e0 la suppression de la pr\u00e9sentation de l'antig\u00e8ne de sa cellule d'origine - RVH-Synergie.org<\/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:\/\/rvh-synergie.org\/actualites\/limmunogenicite-faible-du-carcinome-basal-lie-a-la-suppression-de-la-presentation-de-lantigene-de-sa-cellule-dorigine\/\" \/>\n<meta property=\"og:locale\" content=\"fr_FR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"L'immunog\u00e9nicit\u00e9 faible du carcinome basal li\u00e9 \u00e0 la suppression de la pr\u00e9sentation de l'antig\u00e8ne de sa cellule d'origine - 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