{"id":44199,"date":"2025-09-26T18:59:17","date_gmt":"2025-09-26T16:59:17","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/09\/26\/efficient-expansion-of-tumor-infiltrating-lymphocytes-from-gynecologic-cancer\/"},"modified":"2025-09-26T18:59:17","modified_gmt":"2025-09-26T16:59:17","slug":"efficient-expansion-of-tumor-infiltrating-lymphocytes-from-gynecologic-cancer","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/09\/26\/efficient-expansion-of-tumor-infiltrating-lymphocytes-from-gynecologic-cancer\/","title":{"rendered":"Efficient expansion of tumor-infiltrating lymphocytes from gynecologic cancer"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Sep 26:vkaf259. doi: 10.1093\/jimmun\/vkaf259. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Tumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive immunotherapy potentially applicable to many types of solid tumors. Although gynecologic malignancies are promising targets for TIL therapy, its objective efficacy has not been established. Current TIL culture typically involves incubation of dissociated samples with high-dose IL-2 (HD-IL2) for weeks to enrich tumor-reactive T cells. While this protocol has been successfully used for melanoma TIL, it has not necessarily been optimized for other cancers. Here we investigated the method of efficiently expanding TILs derived from patients with gynecological cancers. TILs were incubated with HD-IL2 (HD-IL2-TILs) or stimulated with K562 cells expressing anti-CD3 mAb and CD80 (\u03b1CD3\/CD80-TILs). We found that the \u03b1CD3\/CD80-TILs showed significantly better proliferation than HD-IL2-TILs. The TIL populations that predominantly expanded upon \u03b1CD3\/CD80 stimulation expressed high levels of PD-1 and CD28. CD28 co-stimulation was essential to overcome PD-1-mediated signals for growth suppression. We also identified DUSP4 as a negative regulator of TIL proliferation by downregulating ERK phosphorylation. The \u03b1CD3\/CD80-TILs were reactive to tumor cells as shown by IFN-\u03b3 secretion and CD107a expression. Moreover, the \u03b1CD3\/CD80-TILs were efficiently transduced with a chimeric cytokine receptor that we had previously developed to provide constitutive IL-7 signaling, resulting in superior in vivo persistence and antitumor effects without exogenous cytokine support in mouse models. Collectively, this study shows that direct stimulation of TILs with anti-CD3 mAb and CD28 co-stimulation achieves efficient expansion of tumor-reactive TILs. Genetic engineering of cytokine signaling in TILs may further enhance TIL functions and replace cytokine administration after TIL infusion.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41003760\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250926125917&amp;v=2.18.0.post9+e462414\">41003760<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf259\">10.1093\/jimmun\/vkaf259<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Sep 26:vkaf259. doi: 10.1093\/jimmun\/vkaf259. Online ahead of print. ABSTRACT Tumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive immunotherapy potentially applicable to many types of solid tumors. Although gynecologic malignancies are promising targets for TIL therapy, its objective efficacy has not been established. Current TIL culture typically involves incubation of dissociated samples &#8230; <a title=\"Efficient expansion of tumor-infiltrating lymphocytes from gynecologic cancer\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/09\/26\/efficient-expansion-of-tumor-infiltrating-lymphocytes-from-gynecologic-cancer\/\" aria-label=\"Read more about Efficient expansion of tumor-infiltrating lymphocytes from gynecologic cancer\">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":[42,71],"tags":[],"class_list":["post-44199","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\/44199","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=44199"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/44199\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=44199"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=44199"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=44199"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}