{"id":71731,"date":"2026-07-29T12:40:10","date_gmt":"2026-07-29T10:40:10","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/07\/29\/nkp44-recognition-of-platelet-derived-growth-factor-d-enhances-the-cytolytic-activity-of-natural-killer-cells\/"},"modified":"2026-07-29T12:40:10","modified_gmt":"2026-07-29T10:40:10","slug":"nkp44-recognition-of-platelet-derived-growth-factor-d-enhances-the-cytolytic-activity-of-natural-killer-cells","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/07\/29\/nkp44-recognition-of-platelet-derived-growth-factor-d-enhances-the-cytolytic-activity-of-natural-killer-cells\/","title":{"rendered":"NKp44 recognition of platelet-derived growth factor D enhances the cytolytic activity of natural killer cells"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2026 Jul 10;215(7):vkag204. doi: 10.1093\/jimmun\/vkag204.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Natural killer (NK) cells are cytotoxic innate lymphoid cells that play a critical role in tumor surveillance by releasing proinflammatory cytokines and cytotoxic granules. NKp44 is an activating receptor that promotes NK cell secretion of TNF and IFN-\u03b3 upon engaging platelet-derived growth factor D (PDGF-DD), a ligand frequently overexpressed in aggressive malignancies, such as glioblastoma (GBM). However, whether NKp44-mediated recognition of PDGF-DD can directly enhance NK cell cytotoxicity against tumor cells remains unclear. Here we investigated the effect of PDGF-DD stimulation on NK cell cytotoxicity by analyzing the activity of cytotoxic transcriptional programs and cytolytic function of human NK cells in flow cytometry-based cytotoxicity assays. We demonstrate that PDGF-DD stimulation of NKp44 activates a procytotoxic transcriptional program and secretion of key cytotoxic effectors, including granzyme B, perforin, and Fas ligand. This response significantly enhanced NK cell-mediated cytotoxicity of GBM cell lines (T98G, U87, LN229 and A172) and HEK 293T cells, but not the NK-sensitive K562 cell line. Furthermore, the negation of PDGF-DD-mediated cytotoxicity and lytic granule secretion upon blockade and genetic ablation of NKp44 reveal that PDGF-DD augmentation of NK cell tumoricidal activity is tumor-type specific and reliant upon NKp44. Our data highlight a novel mechanism by which NK cells can detect soluble components of the tumor secretome, expanding the paradigm of NK cell activation beyond classical cell-surface interactions.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42522261\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20260729064009&amp;v=2.20.0\">42522261<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkag204\">10.1093\/jimmun\/vkag204<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2026 Jul 10;215(7):vkag204. doi: 10.1093\/jimmun\/vkag204. ABSTRACT Natural killer (NK) cells are cytotoxic innate lymphoid cells that play a critical role in tumor surveillance by releasing proinflammatory cytokines and cytotoxic granules. NKp44 is an activating receptor that promotes NK cell secretion of TNF and IFN-\u03b3 upon engaging platelet-derived growth factor D (PDGF-DD), a ligand &#8230; <a title=\"NKp44 recognition of platelet-derived growth factor D enhances the cytolytic activity of natural killer cells\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/07\/29\/nkp44-recognition-of-platelet-derived-growth-factor-d-enhances-the-cytolytic-activity-of-natural-killer-cells\/\" aria-label=\"Read more about NKp44 recognition of platelet-derived growth factor D enhances the cytolytic activity of natural killer cells\">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":[42,71],"tags":[],"class_list":["post-71731","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\/71731","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=71731"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/71731\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=71731"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=71731"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=71731"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}