{"id":76965,"date":"2026-09-21T17:54:43","date_gmt":"2026-09-21T15:54:43","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/09\/21\/il-21-boosts-t-cell-therapy-efficacy-for-solid-tumors-by-enhancing-mitochondrial-ca2-mediated-motility-of-effector-cd8-t-cells\/"},"modified":"2026-09-21T17:54:43","modified_gmt":"2026-09-21T15:54:43","slug":"il-21-boosts-t-cell-therapy-efficacy-for-solid-tumors-by-enhancing-mitochondrial-ca2-mediated-motility-of-effector-cd8-t-cells","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/09\/21\/il-21-boosts-t-cell-therapy-efficacy-for-solid-tumors-by-enhancing-mitochondrial-ca2-mediated-motility-of-effector-cd8-t-cells\/","title":{"rendered":"IL-21 boosts T cell-therapy efficacy for solid tumors by enhancing mitochondrial Ca2+-mediated motility of effector CD8+ T cells"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 Sep 21. doi: 10.1158\/2326-6066.CIR-26-0401. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Cell motility, characterized by random walk and exploratory search movement, enables effector CD8+ T cells to search for sparse antigen-specific cancer targets within a tumor. This is of special relevance for treatment of solid cancers with adoptive T-cell receptor (TCR) T-cell therapy, where administered effector CD8+ T cells recognize specific MHC-I-presented antigens. Cell motility requires cytoskeleton remodeling to facilitate shape changes and movement. Herein, we show that increased mitochondrial Ca2+ levels are essential to reduce cytoskeleton stiffness of effector CD8+ T cells, leading to acquisition of a polarized shape and high motility. IL-21, but not IL-7 or IL-15, was able to raise mitochondrial Ca2+ levels in effector CD8+ T cells and increase their motility without affecting survival and proliferation. This increase in mitochondrial Ca2+ levels triggered by IL-21 was driven by sustaining mitochondrial membrane potential through mitochondrial STAT3, independently of its transcriptional activity. Enhanced motility of effector CD8+ T cells led to a superior killing efficacy of antigen-specific melanoma cells in vitro. Furthermore, enhanced mitochondrial Ca2+-mediated motility of adoptive TCR-specific effector CD8+ T cells resulted in a superior antitumor efficacy of this treatment against solid tumors in vivo. Thus, enhancing effector CD8+ T-cell motility is a promising strategy to boost efficacy of adoptive T-cell therapies against solid tumors.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42765849\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260921115443&amp;v=2.20.1\">42765849<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-26-0401\">10.1158\/2326-6066.CIR-26-0401<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 Sep 21. doi: 10.1158\/2326-6066.CIR-26-0401. Online ahead of print. ABSTRACT Cell motility, characterized by random walk and exploratory search movement, enables effector CD8+ T cells to search for sparse antigen-specific cancer targets within a tumor. This is of special relevance for treatment of solid cancers with adoptive T-cell receptor (TCR) T-cell therapy, &#8230; <a title=\"IL-21 boosts T cell-therapy efficacy for solid tumors by enhancing mitochondrial Ca2+-mediated motility of effector CD8+ T cells\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/09\/21\/il-21-boosts-t-cell-therapy-efficacy-for-solid-tumors-by-enhancing-mitochondrial-ca2-mediated-motility-of-effector-cd8-t-cells\/\" aria-label=\"Read more about IL-21 boosts T cell-therapy efficacy for solid tumors by enhancing mitochondrial Ca2+-mediated motility of effector CD8+ T 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":[55,42],"tags":[],"class_list":["post-76965","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\/76965","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=76965"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/76965\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=76965"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=76965"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=76965"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}