{"id":71386,"date":"2026-07-24T01:09:49","date_gmt":"2026-07-23T23:09:49","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/07\/24\/tlr-mediated-calcium-signaling-regulates-killing-capacity-of-expanded-nk-cells-challenges-for-potential-aml-immunotherapyvojtech-graman-on-23-de-july-de-2026-at-1000\/"},"modified":"2026-07-24T01:09:49","modified_gmt":"2026-07-23T23:09:49","slug":"tlr-mediated-calcium-signaling-regulates-killing-capacity-of-expanded-nk-cells-challenges-for-potential-aml-immunotherapyvojtech-graman-on-23-de-july-de-2026-at-1000","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/07\/24\/tlr-mediated-calcium-signaling-regulates-killing-capacity-of-expanded-nk-cells-challenges-for-potential-aml-immunotherapyvojtech-graman-on-23-de-july-de-2026-at-1000\/","title":{"rendered":"TLR-Mediated Calcium Signaling Regulates Killing Capacity of Expanded NK Cells: Challenges for Potential AML Immunotherapy\u200bVojt\u011bch Graman   on 23 de July de 2026 at 10:00"},"content":{"rendered":"<div>\n<p><b>J Leukoc Biol<\/b>. 2026 Jul 23:qiag092. doi: 10.1093\/jleuko\/qiag092. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Natural killer (NK) cells are central to cancer immunosurveillance and immunotherapy. Their ability to engage in killing is critical for efficient target elimination and depends on tightly regulated Ca2+ signaling controlling granzyme degranulation. TLR engagement has been linked to Ca2+ signaling in other immune cell types, while specific role in NK cells remains unresolved. Given that NK cells express a broad range of TLRs, and that presence of TLR ligands-including damage- and pathogen-associated molecular patterns-can influence clinical scenarios including adoptive NK cell therapy, investigating TLR-driven Ca2+ signaling in NK cells is particularly relevant. Here, we examined how stimulation with selected TLR ligands influences Ca2+ signaling and NK cell activity. Immediate stimulation induced a rapid elevation of cytosolic Ca2+ in expanded NK cells. Functionally, TLR stimulation increased degranulation and enhanced cytotoxicity at high effector-to-target ratios. Under conditions of target excess, however, TLR-treated NK cells displayed impaired killing, likely due to unbalanced Ca2+ levels. These findings demonstrate that TLR signaling directly modulates Ca2+ flux in NK cells and can either potentiate or impair cytotoxic activity depending on context. While clinical implications remain hypothetical, such TLR-driven dysregulation affect NK cell killing activity in the inflammatory or pathogen-rich environments frequently encountered after chemotherapy. Our findings suggest that TLR-Ca2+ impact on cytotoxicity should be considered in adoptive transfer therapies where previous treatment affects systemic levels of TLR ligands, such as in patients with AML, where NK cell immunotherapy is frequently tested in trials.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42490592\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=8405628&amp;ff=20260723190948&amp;v=2.20.0\">42490592<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jleuko\/qiag092\">10.1093\/jleuko\/qiag092<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Leukoc Biol. 2026 Jul 23:qiag092. doi: 10.1093\/jleuko\/qiag092. Online ahead of print. ABSTRACT Natural killer (NK) cells are central to cancer immunosurveillance and immunotherapy. Their ability to engage in killing is critical for efficient target elimination and depends on tightly regulated Ca2+ signaling controlling granzyme degranulation. TLR engagement has been linked to Ca2+ signaling in &#8230; <a title=\"TLR-Mediated Calcium Signaling Regulates Killing Capacity of Expanded NK Cells: Challenges for Potential AML Immunotherapy\u200bVojt\u011bch Graman   on 23 de July de 2026 at 10:00\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/07\/24\/tlr-mediated-calcium-signaling-regulates-killing-capacity-of-expanded-nk-cells-challenges-for-potential-aml-immunotherapyvojtech-graman-on-23-de-july-de-2026-at-1000\/\" aria-label=\"Read more about TLR-Mediated Calcium Signaling Regulates Killing Capacity of Expanded NK Cells: Challenges for Potential AML Immunotherapy\u200bVojt\u011bch Graman   on 23 de July de 2026 at 10:00\">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":[86,42],"tags":[],"class_list":["post-71386","post","type-post","status-publish","format-standard","hentry","category-journal-of-leukocyte-biology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/71386","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=71386"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/71386\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=71386"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=71386"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=71386"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}