{"id":14872,"date":"2022-06-21T11:20:50","date_gmt":"2022-06-21T15:20:50","guid":{"rendered":"https:\/\/themedicalxchange.com\/?p=14872"},"modified":"2022-06-23T15:21:52","modified_gmt":"2022-06-23T19:21:52","slug":"7022_de-nouvelles-donnees-cliniques-confirment-le-role-du-microbiome-intestinal-dans-la-reponse-a-limmunotherapie","status":"publish","type":"post","link":"https:\/\/themedicalxchange.com\/fr\/2022\/06\/21\/7022_de-nouvelles-donnees-cliniques-confirment-le-role-du-microbiome-intestinal-dans-la-reponse-a-limmunotherapie\/","title":{"rendered":"De nouvelles donn\u00e9es cliniques confirment le r\u00f4le du microbiome intestinal dans la r\u00e9ponse \u00e0 l\u2019immunoth\u00e9rapie"},"content":{"rendered":"

L\u2019interaction entre le microbiome intestinal et l\u2019efficacit\u00e9 d\u2019une immunoth\u00e9rapie ax\u00e9e sur le PD-1 fait actuellement l\u2019objet de nombreuses \u00e9tudes \u00e0 la suite des travaux d\u2019avant-garde r\u00e9alis\u00e9s par des chercheurs de l\u2019Institut de lutte contre le cancer Gustave\u00a0Roussy, de Villejuif, en France. Participant de la premi\u00e8re heure \u00e0 ces \u00e9tudes, le Dr\u00a0<\/sup>Bertrand\u00a0Routy, directeur scientifique du Laboratoire d\u2019immunoth\u00e9rapie et d\u2019oncomicrobiome, du Centre de recherche de l\u2019Universit\u00e9 de Montr\u00e9al, est \u00e9galement un des auteurs de l\u2019\u00e9tude dont il est question ici (Miller, W.H., Routy, B., Jamal, R., et al<\/em>. \u00ab\u00a0Fecal microbiota transplantation followed by anti-PD-1 treatment in patients with advanced melanoma\u00a0\u00bb; affiche\u00a09533).<\/p>\n

\u00ab\u00a0C\u2019est un fait \u00e9tabli que le microbiome intestinal est un biomarqueur de la r\u00e9ponse \u00e0 l\u2019immunoth\u00e9rapie chez les patients atteints d\u2019un m\u00e9lanome\u00a0\u00bb, a expliqu\u00e9 une autre des co-auteurs, la Dre<\/sup>\u00a0Arielle\u00a0Elkrief, qui a travaill\u00e9 avec le Dr<\/sup>\u00a0Routy au Centre de recherche de l\u2019Universit\u00e9 de Montr\u00e9al et qui est aujourd\u2019hui charg\u00e9e de recherche au Memorial Sloan Kettering Cancer Center, de New York, NY. Elle a ajout\u00e9 que la greffe f\u00e9cale est l\u2019une des strat\u00e9gies actuellement \u00e0 l\u2019\u00e9tude et que ces travaux visent \u00e0 d\u00e9terminer s\u2019il est possible de modifier le microbiome intestinal afin d\u2019amplifier la r\u00e9ponse aux traitements par ICI.<\/p>\n

Cette \u00e9tude porte sur 20\u00a0patients \u00e2g\u00e9s de 75,5\u00a0ans en moyenne et atteints d\u2019une forme avanc\u00e9e de m\u00e9lanome, qui ont \u00e9t\u00e9 recrut\u00e9s dans 3\u00a0\u00e9tablissements canadiens. Tous sauf 2\u00a0patients en \u00e9taient au stade\u00a04 et le quart d\u2019entre eux \u00e9taient porteurs d\u2019une mutation du g\u00e8ne BRAF<\/em>. Au cours de cette \u00e9tude, le pouvoir immunog\u00e8ne de leurs f\u00e8ces a \u00e9t\u00e9 \u00e9valu\u00e9 avant et apr\u00e8s la greffe f\u00e9cale \u00e0 l\u2019aide d\u2019un mod\u00e8le murin de tumeurs. <\/p>\n

L\u2019\u00e9tude ne comportait pas de groupe t\u00e9moin, mais l\u2019observation d\u2019une activit\u00e9 d\u2019une intensit\u00e9 sans pr\u00e9c\u00e9dent est venue \u00e9tayer l\u2019hypoth\u00e8se de travail, a rapport\u00e9 le Dr<\/sup>\u00a0Wilson H. Miller, professeur \u00e0 la Division de m\u00e9decine exp\u00e9rimentale, de l\u2019universit\u00e9 McGill, \u00e0 Montr\u00e9al, au Qu\u00e9bec.<\/p>\n

Atteinte de l\u2019objectif principal en mati\u00e8re d\u2019innocuit\u00e9<\/strong><\/h2>\n

La greffe f\u00e9cale, r\u00e9alis\u00e9e au moyen de comprim\u00e9s \u00e0 prise orale et choisie express\u00e9ment pour la diversit\u00e9 du microbiote, a \u00e9t\u00e9 bien tol\u00e9r\u00e9e. Certes, plus de la moiti\u00e9 des patients se sont plaints d\u2019effets ind\u00e9sirables de nature digestive comme de la diarrh\u00e9e et des malaises abdominaux, mais ils \u00e9taient tous de grade 1. Deux patients ont mis fin \u00e0 leur traitement par l\u2019ICI en raison d\u2019effets ind\u00e9sirables, mais aucun d\u2019eux n\u2019\u00e9tait consid\u00e9r\u00e9 comme grave \u00a0(Figure 1<\/a>).<\/p>\n

Le recours \u00e0 la greffe f\u00e9cale une semaine avant le traitement anti-PD-1 s\u2019est traduit par un taux de r\u00e9ponse objective (TRO) de 65\u00a0% (13\u00a0patients sur 20). Selon le Dr<\/sup> Miller, trois d\u2019entre eux ont obtenu une r\u00e9ponse compl\u00e8te (RC)<\/p>\n

En plus de ce TRO relativement \u00e9lev\u00e9 dans un effectif de sujets aux prises avec une maladie avanc\u00e9e, il faut savoir que 75\u00a0% d\u2019entre eux ont retir\u00e9 des bienfaits cliniques sous la forme d\u2019une stabilisation de leur maladie ou mieux encore pendant au moins 6\u00a0mois. La survie sans progression m\u00e9diane dans cet effectif n\u2019est toujours pas \u00e9tablie apr\u00e8s un suivi m\u00e9dian de 11,2\u00a0mois.<\/p>\n

Notons qu\u2019une r\u00e9gulation positive de l\u2019interleukine\u00a017 (IL-17) a \u00e9t\u00e9 mise en corr\u00e9lation avec une augmentation du nombre de cellules\u00a0Th17 dans le sang p\u00e9riph\u00e9rique apr\u00e8s la greffe f\u00e9cale, ce qui est vu comme le signe d\u2019une activit\u00e9 immunitaire plus intense, un \u00e9l\u00e9ment essentiel pour que les bienfaits de l\u2019ICI se concr\u00e9tisent.<\/p>\n

Le mod\u00e8le murin a \u00e9tay\u00e9 les observations cliniques. Lorsque les tumeurs murines ont \u00e9t\u00e9 expos\u00e9es aux f\u00e8ces des patients recueillies avant la greffe f\u00e9cale, leur sensibilit\u00e9 \u00e0 l\u2019\u00e9gard de l\u2019ICI restait faible. Apr\u00e8s la greffe, une sensibilisation a \u00e9t\u00e9 observ\u00e9e, mais seulement avec les f\u00e8ces recueillies chez des patients ayant r\u00e9pondu au traitement par l\u2019ICI. <\/p>\n

Conclusion<\/strong><\/h2>\n

Le principal r\u00e9sultat de cette \u00e9tude, c\u2019est que la greffe f\u00e9cale suivie d\u2019un traitement anti-PD-1 est s\u00fbre. Cela dit, l\u2019activit\u00e9 de l\u2019ICI apr\u00e8s la greffe f\u00e9cale est en phase avec le corpus croissant de donn\u00e9es probantes montrant que la sant\u00e9 du microbiome intestinale a une influence sur la capacit\u00e9 du syst\u00e8me immunitaire \u00e0 r\u00e9pondre aux immunoth\u00e9rapies. <\/p>\n

Le Dr<\/sup>\u00a0Miller reconna\u00eet que cette \u00e9tude a \u00e9t\u00e9 men\u00e9e chez un petit nombre de sujets, mais il pr\u00e9cise que les donn\u00e9es recueillies valident le principe voulant que la sant\u00e9 du microbiome intestinal soit importante pour l\u2019activit\u00e9 de l\u2019immunoth\u00e9rapie. Il a ajout\u00e9 que ce travail \u00ab\u00a0pave la voie aux futures interventions ax\u00e9es sur le microbiome\u00a0\u00bb, qui pourraient favoriser l\u2019obtention d\u2019une r\u00e9ponse aux ICI ou \u00e0 d\u2019autres immunoth\u00e9rapies.<\/p>\n","protected":false},"excerpt":{"rendered":"

Chicago \u2013 <\/b>Un corpus croissant de donn\u00e9es probantes issues d\u2019une s\u00e9rie d\u2019\u00e9tudes r\u00e9centes, dont une \u00e9tude clinique de petite envergure, mais convaincante pr\u00e9sent\u00e9e lors de la r\u00e9union annuelle de 2022 de l\u2019ASCO, porte \u00e0 croire que la sant\u00e9 du microbiome intestinal joue un r\u00f4le essentiel dans le d\u00e9clenchement de la r\u00e9ponse \u00e0 un traitement par un inhibiteur de points de contr\u00f4le (ICI). Cette \u00e9tude de phase I visait avant tout \u00e0 \u00e9valuer l\u2019innocuit\u00e9 d\u2019une greffe f\u00e9cale chez des patients atteints d\u2019un m\u00e9lanome de stade 4 avant qu\u2019ils entreprennent un traitement par un ICI dirig\u00e9 contre le r\u00e9cepteur de mort cellulaire programm\u00e9e 1 (PD-1). C\u2019est un fait reconnu que la greffe f\u00e9cale am\u00e9liore la diversit\u00e9 du microbiote, une des grandes caract\u00e9ristiques d\u2019un microbiome intestinal sain. Les signes d\u2019efficacit\u00e9 comptaient parmi les param\u00e8tres d\u2019\u00e9valuation secondaires.<\/p>\n","protected":false},"author":9,"featured_media":14895,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"tags":[757,417,797,798],"class_list":["post-14872","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","tag-2022-fr","tag-asco-fr","tag-immunotherapie","tag-melanome","area_tag-oncologie"],"acf":[],"yoast_head":"\nDe nouvelles donn\u00e9es cliniques confirment le r\u00f4le du microbiome intestinal dans la r\u00e9ponse \u00e0 l\u2019immunoth\u00e9rapie - The Medical Xchange<\/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:\/\/themedicalxchange.com\/fr\/2022\/06\/21\/7022_de-nouvelles-donnees-cliniques-confirment-le-role-du-microbiome-intestinal-dans-la-reponse-a-limmunotherapie\/\" \/>\n<meta property=\"og:locale\" content=\"fr_FR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"De nouvelles donn\u00e9es cliniques confirment le r\u00f4le du microbiome intestinal dans la r\u00e9ponse \u00e0 l\u2019immunoth\u00e9rapie - The Medical Xchange\" \/>\n<meta property=\"og:description\" content=\"Chicago \u2013 Un corpus croissant de donn\u00e9es probantes issues d\u2019une s\u00e9rie d\u2019\u00e9tudes r\u00e9centes, dont une \u00e9tude clinique de petite envergure, mais convaincante pr\u00e9sent\u00e9e lors de la r\u00e9union annuelle de 2022 de l\u2019ASCO, porte \u00e0 croire que la sant\u00e9 du microbiome intestinal joue un r\u00f4le essentiel dans le d\u00e9clenchement de la r\u00e9ponse \u00e0 un traitement par un inhibiteur de points de contr\u00f4le (ICI). 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Cette \u00e9tude de phase I visait avant tout \u00e0 \u00e9valuer l\u2019innocuit\u00e9 d\u2019une greffe f\u00e9cale chez des patients atteints d\u2019un m\u00e9lanome de stade 4 avant qu\u2019ils entreprennent un traitement par un ICI dirig\u00e9 contre le r\u00e9cepteur de mort cellulaire programm\u00e9e 1 (PD-1). C\u2019est un fait reconnu que la greffe f\u00e9cale am\u00e9liore la diversit\u00e9 du microbiote, une des grandes caract\u00e9ristiques d\u2019un microbiome intestinal sain. 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