{"id":29870,"date":"2025-04-10T18:49:11","date_gmt":"2025-04-10T16:49:11","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/04\/10\/the-trib2-dnmt1-pathway-generates-an-immune-cold-microenvironment-in-glioblastoma-and-its-inhibition-promotes-immunotherapy\/"},"modified":"2025-04-10T18:49:11","modified_gmt":"2025-04-10T16:49:11","slug":"the-trib2-dnmt1-pathway-generates-an-immune-cold-microenvironment-in-glioblastoma-and-its-inhibition-promotes-immunotherapy","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/04\/10\/the-trib2-dnmt1-pathway-generates-an-immune-cold-microenvironment-in-glioblastoma-and-its-inhibition-promotes-immunotherapy\/","title":{"rendered":"The TRIB2-DNMT1 pathway generates an immune cold microenvironment in glioblastoma and its inhibition promotes immunotherapy"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Apr 10. doi: 10.1158\/2326-6066.CIR-24-0807. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>The lack of response of glioblastoma (GBM) to immunotherapy is closely related to the limited number of T cells in the tumor microenvironment (TME). However, it is still not known why GBM is characterized by an immune-cold TME with reduced CD8+ T-cell infiltration when there is substantial myeloid cell infiltration and a substantial alteration of the blood-brain barrier. The aim of this study was to identify regulators of low CD8+ T-cell infiltration in GBM. Using transcriptomic screening, we found that TRIB2 is a regulator of the immune-cold microenvironment characteristic of GBM. Further analysis of a cohort of 114 brain tumors with immunohistochemistry, RNA-sequencing and quantitative real-time PCR, showed that TRIB2 inhibited the transcription of genes involved in antigen presentation by the tumor cells and of genes involved in T-cell recruitment by modulating expression of methylation regulators, in particular DNMT1. Further, we observed 75% survival after TRIB2 inhibition in murine glioma models and showed transcriptomic reprogramming by Decitabine of genes involved in the processes described above. In our patient-derived tumor fragments assay we observed a consistent generalized response to decitabine, suggesting that DNMT1 inhibition could be a promising therapeutic strategy for GBM.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40208240\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250410124910&amp;v=2.18.0.post9+e462414\">40208240<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-0807\">10.1158\/2326-6066.CIR-24-0807<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Apr 10. doi: 10.1158\/2326-6066.CIR-24-0807. Online ahead of print. ABSTRACT The lack of response of glioblastoma (GBM) to immunotherapy is closely related to the limited number of T cells in the tumor microenvironment (TME). However, it is still not known why GBM is characterized by an immune-cold TME with reduced CD8+ T-cell &#8230; <a title=\"The TRIB2-DNMT1 pathway generates an immune cold microenvironment in glioblastoma and its inhibition promotes immunotherapy\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/04\/10\/the-trib2-dnmt1-pathway-generates-an-immune-cold-microenvironment-in-glioblastoma-and-its-inhibition-promotes-immunotherapy\/\" aria-label=\"Read more about The TRIB2-DNMT1 pathway generates an immune cold microenvironment in glioblastoma and its inhibition promotes immunotherapy\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-29870","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\/29870","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"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=29870"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/29870\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=29870"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=29870"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=29870"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}