{"id":17188,"date":"2024-10-05T12:14:10","date_gmt":"2024-10-05T10:14:10","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2024\/10\/05\/transient-ezh2-suppression-by-tazemetostat-during-in-vitro-expansion-maintains-t-cell-stemness-and-improves-adoptive-t-cell-therapy\/"},"modified":"2024-10-05T12:14:10","modified_gmt":"2024-10-05T10:14:10","slug":"transient-ezh2-suppression-by-tazemetostat-during-in-vitro-expansion-maintains-t-cell-stemness-and-improves-adoptive-t-cell-therapy","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2024\/10\/05\/transient-ezh2-suppression-by-tazemetostat-during-in-vitro-expansion-maintains-t-cell-stemness-and-improves-adoptive-t-cell-therapy\/","title":{"rendered":"Transient EZH2 suppression by Tazemetostat during in vitro expansion maintains T-cell stemness and improves adoptive T-cell therapy"},"content":{"rendered":"<div>\n<p>Cancer Immunol Res. 2024 Oct 4. doi: 10.1158\/2326-6066.CIR-24-0089. Online ahead of print.<\/p>\n<p>ABSTRACT<\/p>\n<p>The histone methyltransferase enhancer of zeste homolog 2 (EZH2) plays important roles in T-cell differentiation, proliferation and function. Previous studies have demonstrated that genetic deletion of EZH2 in CD8+ or total T cells impairs their antiviral and antitumor activity, cytokine production and ability to expand upon rechallenge. Contrary to the detrimental role of deleting T cell-intrinsic EZH2, here we have demonstrated that transient inhibition of EZH2 in T cells prior to the phenotypic onset of exhaustion with a clinically approved inhibitor, Tazemetostat, delayed their dysfunctional progression and preserved T-cell stemness and polyfunctionality but had no negative impact on cell proliferation. Tazemetostat induced T-cell epigenetic reprogramming and increased the expression of the self-renewal T-cell transcription factor TCF1 by reducing H3K27 methylation at its promoter preferentially in rapidly dividing T cells. In a murine melanoma model, T cells depleted of EZH2 induced poor tumor control, whereas adoptively transferred T cells pretreated with tazemetostat exhibited superior antitumor immunity, especially when used in combination with anti-PD-1 blockade. Collectively, these data highlight the potential of transient epigenetic reprogramming by EZH2 inhibition to enhance adoptive T-cell immunotherapy.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39365901\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20241005061409&amp;v=2.18.0.post9+e462414\">39365901<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-0089\">10.1158\/2326-6066.CIR-24-0089<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2024 Oct 4. doi: 10.1158\/2326-6066.CIR-24-0089. Online ahead of print. ABSTRACT The histone methyltransferase enhancer of zeste homolog 2 (EZH2) plays important roles in T-cell differentiation, proliferation and function. Previous studies have demonstrated that genetic deletion of EZH2 in CD8+ or total T cells impairs their antiviral and antitumor activity, cytokine production and &#8230; <a title=\"Transient EZH2 suppression by Tazemetostat during in vitro expansion maintains T-cell stemness and improves adoptive T-cell therapy\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2024\/10\/05\/transient-ezh2-suppression-by-tazemetostat-during-in-vitro-expansion-maintains-t-cell-stemness-and-improves-adoptive-t-cell-therapy\/\" aria-label=\"Read more about Transient EZH2 suppression by Tazemetostat during in vitro expansion maintains T-cell stemness and improves adoptive T-cell therapy\">Read more<\/a><\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-17188","post","type-post","status-publish","format-standard","hentry","category-cancer-immunology-reserch","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/17188","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=17188"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/17188\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=17188"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=17188"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=17188"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}