{"id":40441,"date":"2025-08-13T06:47:59","date_gmt":"2025-08-13T04:47:59","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/08\/13\/activation-and-exhaustion-of-cd8-t-cells-in-patients-with-chronic-lymphocytic-leukemia-treated-with-ibrutinib-and-pembrolizumab\/"},"modified":"2025-08-13T06:47:59","modified_gmt":"2025-08-13T04:47:59","slug":"activation-and-exhaustion-of-cd8-t-cells-in-patients-with-chronic-lymphocytic-leukemia-treated-with-ibrutinib-and-pembrolizumab","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/08\/13\/activation-and-exhaustion-of-cd8-t-cells-in-patients-with-chronic-lymphocytic-leukemia-treated-with-ibrutinib-and-pembrolizumab\/","title":{"rendered":"Activation and exhaustion of CD8 T cells in patients with chronic lymphocytic leukemia treated with ibrutinib and pembrolizumab"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Aug 12:vkaf182. doi: 10.1093\/jimmun\/vkaf182. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Immune checkpoint blockade has been shown to restore anti-tumor T-cell function and elicit durable responses in select solid and hematopoietic malignancies. However, single-agent anti-programmed death 1 (PD-1) antibodies proved less efficacious in patients with chronic lymphocytic leukemia (CLL). In patients with high-risk or relapsed\/refractory CLL, we conducted a phase 2 study testing the combination of lead-in ibrutinib and up to 2 cycles of fludarabine, followed by continuous therapy with ibrutinib and 17 cycles of pembrolizumab administered every 3 weeks. A total of 15 patients were enrolled. In 10 patients evaluable for response, we observed 1 complete response and 9 partial responses. There was no discernible benefit of the combination beyond what is expected from ibrutinib monotherapy. However, 3 weeks after the first dose of pembrolizumab, we detected CD8 T-cell proliferation in a subset of patients, whom we called &#8220;immune responders.&#8221; In the responders, CD27-expressing CD8 T cells were relatively increased over immune nonresponders. Paired single-cell RNA and TCR sequencing revealed clonal expansion of activated GZMK+ CD8 effector memory and terminally differentiated effector cells. After 6 months of pembrolizumab treatment, the proportion of activated and proliferating CD8 T cells returned to baseline levels. Similarly, most novel clonotypes identified after 1 cycle of pembrolizumab decreased in frequency on long-term treatment. In summary, pembrolizumab did not improve the clinical response over ibrutinib monotherapy but transiently activated distinct clonotypes of CD8 T cells in a subset of CLL patients.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40796313\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250813004755&amp;v=2.18.0.post9+e462414\">40796313<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf182\">10.1093\/jimmun\/vkaf182<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Aug 12:vkaf182. doi: 10.1093\/jimmun\/vkaf182. Online ahead of print. ABSTRACT Immune checkpoint blockade has been shown to restore anti-tumor T-cell function and elicit durable responses in select solid and hematopoietic malignancies. However, single-agent anti-programmed death 1 (PD-1) antibodies proved less efficacious in patients with chronic lymphocytic leukemia (CLL). In patients with high-risk or &#8230; <a title=\"Activation and exhaustion of CD8 T cells in patients with chronic lymphocytic leukemia treated with ibrutinib and pembrolizumab\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/08\/13\/activation-and-exhaustion-of-cd8-t-cells-in-patients-with-chronic-lymphocytic-leukemia-treated-with-ibrutinib-and-pembrolizumab\/\" aria-label=\"Read more about Activation and exhaustion of CD8 T cells in patients with chronic lymphocytic leukemia treated with ibrutinib and pembrolizumab\">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":[42,71],"tags":[],"class_list":["post-40441","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/40441","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=40441"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/40441\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=40441"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=40441"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=40441"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}