{"id":22738,"date":"2025-01-18T01:14:13","date_gmt":"2025-01-18T00:14:13","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/01\/18\/prdm1-is-a-key-regulator-of-the-natural-killer-t-cell-central-memory-program-and-effector-function\/"},"modified":"2025-01-18T01:14:13","modified_gmt":"2025-01-18T00:14:13","slug":"prdm1-is-a-key-regulator-of-the-natural-killer-t-cell-central-memory-program-and-effector-function","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/01\/18\/prdm1-is-a-key-regulator-of-the-natural-killer-t-cell-central-memory-program-and-effector-function\/","title":{"rendered":"PRDM1 is a key regulator of the natural killer T-cell central memory program and effector function"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Jan 16. doi: 10.1158\/2326-6066.CIR-24-0259. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Natural killer T cells (NKTs) are a promising platform for cancer immunotherapy, but few genes involved in regulation of NKT therapeutic activity have been identified. To find regulators of NKT functional fitness, we developed a CRISPR\/Cas9-based mutagenesis screen that employs a guide RNA (gRNA) library targeting 1,118 immune-related genes. Unmodified NKTs and NKTs expressing a GD2-specific chimeric antigen receptor (GD2.CAR) were transduced with the gRNA library and exposed to CD1d+ leukemia or CD1d-GD2+ neuroblastoma cells, respectively, over six challenge cycles in vitro. Quantification of gRNA abundance revealed enrichment of PRDM1-specific gRNAs in both NKTs and GD2.CAR NKTs, a result that was validated through targeted PRDM1 knockout. Transcriptional, phenotypic, and functional analyses demonstrated that CAR NKTs with PRDM1 knockout underwent central memory-like differentiation and resisted exhaustion. However, these cells downregulated the cytotoxic mediator granzyme B and showed reduced in vitro cytotoxicity and only moderate in vivo antitumor activity in a xenogeneic neuroblastoma model. In contrast, shRNA-mediated PRDM1 knockdown preserved effector function while promoting central memory differentiation, resulting in GD2.CAR NKTs with potent in vivo antitumor activity. Thus, we have identified PRDM1 as a regulator of NKT memory differentiation and effector function that can be exploited to improve the efficacy of NKT-based cancer immunotherapies.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39820712\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250117191412&amp;v=2.18.0.post9+e462414\">39820712<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-0259\">10.1158\/2326-6066.CIR-24-0259<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Jan 16. doi: 10.1158\/2326-6066.CIR-24-0259. Online ahead of print. ABSTRACT Natural killer T cells (NKTs) are a promising platform for cancer immunotherapy, but few genes involved in regulation of NKT therapeutic activity have been identified. To find regulators of NKT functional fitness, we developed a CRISPR\/Cas9-based mutagenesis screen that employs a guide &#8230; <a title=\"PRDM1 is a key regulator of the natural killer T-cell central memory program and effector function\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/01\/18\/prdm1-is-a-key-regulator-of-the-natural-killer-t-cell-central-memory-program-and-effector-function\/\" aria-label=\"Read more about PRDM1 is a key regulator of the natural killer T-cell central memory program and effector function\">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-22738","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\/22738","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=22738"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/22738\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=22738"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=22738"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=22738"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}