{"id":66507,"date":"2026-06-09T01:49:30","date_gmt":"2026-06-08T23:49:30","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/06\/09\/ilt2-identifies-an-unexploited-pool-of-intratumoral-cd8-bystander-t-cells-with-tcr-independent-cytotoxicity-in-renal-cell-carcinoma\/"},"modified":"2026-06-09T01:49:30","modified_gmt":"2026-06-08T23:49:30","slug":"ilt2-identifies-an-unexploited-pool-of-intratumoral-cd8-bystander-t-cells-with-tcr-independent-cytotoxicity-in-renal-cell-carcinoma","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/06\/09\/ilt2-identifies-an-unexploited-pool-of-intratumoral-cd8-bystander-t-cells-with-tcr-independent-cytotoxicity-in-renal-cell-carcinoma\/","title":{"rendered":"ILT2 identifies an unexploited pool of intratumoral CD8+ bystander T cells with TCR-independent cytotoxicity in renal cell carcinoma"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 Jun 8. doi: 10.1158\/2326-6066.CIR-25-1109. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Immune checkpoint inhibitors (ICIs) have improved clear-cell renal cell carcinoma (ccRCC) therapy, yet many patients remain unresponsive. Alternative strategies are needed, and the HLA-G\/ILT2 axis has emerged as a promising immunosuppressive pathway. Here, we deeply characterized CD8\u207aILT2\u207a tumor-infiltrating lymphocytes (TILs) as a distinct subset from CD8\u207aPD1\u207a TILs in ccRCC, using high-dimensional spectral flow cytometry, single-cell transcriptomics, and TCR clonotype analysis. CD8\u207aILT2\u207a TILs were terminally differentiated, highly cytotoxic &#8220;bystander&#8221; cells, enriched for virus-specific TCRs. They phenotypically, transcriptionally and functionally mirrored their circulating counterparts, suggesting peripheral recruitment. In dynamic co-culture assays, they exhibited potent TCR-independent cytotoxicity, mediated by activating innate receptors, namely NKG2D. However, HLA-G inhibited this activity, underscoring the immune-evasive role of the HLA-G\/ILT2 axis. Our study defines CD8\u207aILT2\u207a TILs as an untapped effector population with potential antitumor activity and a promising therapeutic target in ccRCC. These findings offer new insights into TIL functional diversity and pave the way for innovative immunotherapies beyond conventional ICIs.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42258315\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260608194929&amp;v=2.20.0\">42258315<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-1109\">10.1158\/2326-6066.CIR-25-1109<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 Jun 8. doi: 10.1158\/2326-6066.CIR-25-1109. Online ahead of print. ABSTRACT Immune checkpoint inhibitors (ICIs) have improved clear-cell renal cell carcinoma (ccRCC) therapy, yet many patients remain unresponsive. Alternative strategies are needed, and the HLA-G\/ILT2 axis has emerged as a promising immunosuppressive pathway. Here, we deeply characterized CD8\u207aILT2\u207a tumor-infiltrating lymphocytes (TILs) as a &#8230; <a title=\"ILT2 identifies an unexploited pool of intratumoral CD8+ bystander T cells with TCR-independent cytotoxicity in renal cell carcinoma\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/06\/09\/ilt2-identifies-an-unexploited-pool-of-intratumoral-cd8-bystander-t-cells-with-tcr-independent-cytotoxicity-in-renal-cell-carcinoma\/\" aria-label=\"Read more about ILT2 identifies an unexploited pool of intratumoral CD8+ bystander T cells with TCR-independent cytotoxicity in renal cell carcinoma\">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":[55,42],"tags":[],"class_list":["post-66507","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\/66507","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=66507"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/66507\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=66507"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=66507"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=66507"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}