{"id":51554,"date":"2025-12-19T12:40:31","date_gmt":"2025-12-19T11:40:31","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/12\/19\/progenitor-predominant-exhaustion-in-ciks-reveals-tim-3-as-a-superior-target-for-enhancing-cik-cytotoxicityjian-wang-on-19-de-december-de-2025-at-1100\/"},"modified":"2025-12-19T12:40:31","modified_gmt":"2025-12-19T11:40:31","slug":"progenitor-predominant-exhaustion-in-ciks-reveals-tim-3-as-a-superior-target-for-enhancing-cik-cytotoxicityjian-wang-on-19-de-december-de-2025-at-1100","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/12\/19\/progenitor-predominant-exhaustion-in-ciks-reveals-tim-3-as-a-superior-target-for-enhancing-cik-cytotoxicityjian-wang-on-19-de-december-de-2025-at-1100\/","title":{"rendered":"Progenitor-Predominant Exhaustion in CIKs Reveals TIM-3 as a Superior Target for Enhancing CIK Cytotoxicity\u200bJian Wang on 19 de December de 2025 at 11:00"},"content":{"rendered":"
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J Leukoc Biol<\/b>. 2025 Dec 19:qiaf180. doi: 10.1093\/jleuko\/qiaf180. Online ahead of print.<\/p>\n

ABSTRACT<\/b><\/p>\n

Precursor exhausted and terminally exhausted T cells (Tpex and Tex) are associated with immune checkpoints, T-cell checkpoint blockade may improve patient survival. We assessed cytotoxic activity and PD-1\/TIM-3 expressions of CD3+CD8+CD56+ T cells (NK-like T) in cytokine-induced killer (CIK) cells across exhaustion states. We grouped the NK-like T cells into three based on TOX and TCF1 expressions: TOX-TCF1+ (memory-like NK-like T), TOX+TCF1+ (NK-like Tpex), and TOX+TCF1- (NK-like Tex). The proportion of NK-like Tpex cells among the CIK cells was the highest \uff08>90%) after culture. TIM-3 and PD-1 expression were high in NK-like Tpex but low in NK-like Tex cells. However, TIM-3 expression was higher than PD-1 expression in CIK cells, suggesting that combining CIK cells and TIM-3 inhibitors may have better effects. Perforin, granzyme B, DNAM-1, and NKG2D, which are cytotoxicity biomarkers, were more expressed in NK-like Tpex than in NK-like Tex cells, which implies that NK-like Tpex may still has a strong cytotoxic effect. The CD4\u207a T cell counts and TIM-3 expression level in the NK-like Tpex cells were positively correlated. CD4\u207a T cells may actively sustain progenitor exhaustion, but the mechanisms are unknown. In vitro cytotoxicity assays confirmed that CIK cell-mediated tumor cytotoxicity was significantly enhanced by TIM-3 than by PD-1 blockade. Furthermore, tumor cytotoxicity was greater for CIK cell cultures with higher than those with lower CD4\u207a T cell counts following TIM-3 blockade. This work demonstrates CD4\u207aT cell modulation of progenitor exhaustion in CIK cells and positions TIM-3 blockade to rescue their anti-tumor potential.<\/p>\n

PMID:41414757<\/a> | DOI:10.1093\/jleuko\/qiaf180<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"

J Leukoc Biol. 2025 Dec 19:qiaf180. doi: 10.1093\/jleuko\/qiaf180. Online ahead of print. ABSTRACT Precursor exhausted and terminally exhausted T cells (Tpex and Tex) are associated with immune checkpoints, T-cell checkpoint blockade may improve patient survival. We assessed cytotoxic activity and PD-1\/TIM-3 expressions of CD3+CD8+CD56+ T cells (NK-like T) in cytokine-induced killer (CIK) cells across exhaustion … 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":[86,42],"tags":[],"class_list":["post-51554","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\/51554","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=51554"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/51554\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=51554"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=51554"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=51554"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}