{"id":73604,"date":"2026-08-14T18:42:30","date_gmt":"2026-08-14T16:42:30","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/08\/14\/tim3-blockade-with-hypomethylating-therapy-restores-nk-cell-and-cytotoxic-cd4-t-cell-activity-in-patients-with-aml-or-mds\/"},"modified":"2026-08-14T18:42:30","modified_gmt":"2026-08-14T16:42:30","slug":"tim3-blockade-with-hypomethylating-therapy-restores-nk-cell-and-cytotoxic-cd4-t-cell-activity-in-patients-with-aml-or-mds","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/08\/14\/tim3-blockade-with-hypomethylating-therapy-restores-nk-cell-and-cytotoxic-cd4-t-cell-activity-in-patients-with-aml-or-mds\/","title":{"rendered":"TIM3 blockade with hypomethylating therapy restores NK-cell and cytotoxic CD4+ T-cell activity in patients with AML or MDS"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 Aug 14. doi: 10.1158\/2326-6066.CIR-26-0160. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Occasional complete responses to immune checkpoint inhibitor therapy demonstrate that acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) can be immune-sensitive when appropriately targeted. Here, we analyzed AML\/MDS patients (n=14) treated with the anti-TIM3 sabatolimab and the hypomethylating agent decitabine in a phase Ib clinical trial (NCT03066648) using single-cell RNA and T cell receptor (TCR) sequencing (n=6) and functional co-culture assays. Unlike T cell-restricted CTLA4 and PD1, TIM3 was broadly expressed across natural killer (NK)-cell, myeloid-cell, and T-cell populations. Therapy induced expansion of cytotoxic NK-cell subsets and enhanced type I interferon signaling. Fewer than 1% of bone marrow CD8+ T cells displayed a canonical exhaustion phenotype, and treatment preferably expanded small CD8+ T-cell clones in responders. Responders exhibited greater expansion of cytotoxic CD4+ T cells and B cells, as exemplified by a patient with pre-existing CD4+ T-cell large granular lymphocyte leukemia (T-LGLL) achieving an outstanding complete response lasting 23 months. Over 20% of this patient&#8217;s lymphocytes were T-LGLL cells expressing a TCR capable of recognizing autologous blasts. Overall, our results suggest that anti-TIM3 combined with decitabine engages a distinct mechanism of immune activation compared to anti-PD1 and anti-CTLA4, preferentially expanding NK-cell and CD4+ T-cell populations.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42599272\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260814124230&amp;v=2.20.1\">42599272<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-26-0160\">10.1158\/2326-6066.CIR-26-0160<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 Aug 14. doi: 10.1158\/2326-6066.CIR-26-0160. Online ahead of print. ABSTRACT Occasional complete responses to immune checkpoint inhibitor therapy demonstrate that acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) can be immune-sensitive when appropriately targeted. Here, we analyzed AML\/MDS patients (n=14) treated with the anti-TIM3 sabatolimab and the hypomethylating agent decitabine in a &#8230; <a title=\"TIM3 blockade with hypomethylating therapy restores NK-cell and cytotoxic CD4+ T-cell activity in patients with AML or MDS\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/08\/14\/tim3-blockade-with-hypomethylating-therapy-restores-nk-cell-and-cytotoxic-cd4-t-cell-activity-in-patients-with-aml-or-mds\/\" aria-label=\"Read more about TIM3 blockade with hypomethylating therapy restores NK-cell and cytotoxic CD4+ T-cell activity in patients with AML or MDS\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-73604","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\/73604","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=73604"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/73604\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=73604"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=73604"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=73604"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}