{"id":41769,"date":"2025-08-29T18:51:09","date_gmt":"2025-08-29T16:51:09","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/08\/29\/spatiotemporal-immune-landscape-and-long-term-immune-memory-in-pole-mutant-endometrial-cancer-at-the-single-cell-level\/"},"modified":"2025-08-29T18:51:09","modified_gmt":"2025-08-29T16:51:09","slug":"spatiotemporal-immune-landscape-and-long-term-immune-memory-in-pole-mutant-endometrial-cancer-at-the-single-cell-level","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/08\/29\/spatiotemporal-immune-landscape-and-long-term-immune-memory-in-pole-mutant-endometrial-cancer-at-the-single-cell-level\/","title":{"rendered":"Spatiotemporal immune landscape and long-term immune memory in POLE-mutant endometrial cancer at the single-cell level"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Aug 29. doi: 10.1158\/2326-6066.CIR-25-0083. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Polymerase epsilon mutant (POLE-mut) endometrial cancers (EC) are characterized by a near 100% disease-specific survival rate, even when treated by surgery alone. This spectacular survival, combined with the ultramutated genome and high level of neoantigens in these tumors, indicates a substantial degree of immune control in preventing disease spread and recurrence. Although these features are intriguing, the immune infiltration of POLE-mut EC has predominantly been confined to immunohistochemistry studies. Here, we used state of the art single-cell RNA and TCR sequencing to characterize the immune landscape of POLE-mutant ECs. Moreover, we uniquely analyzed patient blood samples taken two to eight years after curative treatment to assess formation of long-term immune memory in circulation. We identified specialized tumor-infiltrating myeloid subsets at different stages of maturation, an array of lymphocytes ranging from immature to cytotoxic and adaptive natural killer (NK) as well as tumor-reactive exhausted and effector T cells, contributing to a highly inflammatory anti-tumor response. Remarkably, our analysis of blood samples taken years after curative treatment uncovered the presence of tumor-reactive T cell clones that matched the primary tumor. This indicates the formation of systemic long-term memory immune responses in POLE-mut EC survivors. Our study highlights the distinctive immunogenicity of POLE-mut EC and identifies key features associated with persistent anti-tumor immunity that may contribute to prolonged, relapse-free survival.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40879333\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250829125106&amp;v=2.18.0.post9+e462414\">40879333<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-0083\">10.1158\/2326-6066.CIR-25-0083<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Aug 29. doi: 10.1158\/2326-6066.CIR-25-0083. Online ahead of print. ABSTRACT Polymerase epsilon mutant (POLE-mut) endometrial cancers (EC) are characterized by a near 100% disease-specific survival rate, even when treated by surgery alone. This spectacular survival, combined with the ultramutated genome and high level of neoantigens in these tumors, indicates a substantial degree &#8230; <a title=\"Spatiotemporal immune landscape and long-term immune memory in POLE-mutant endometrial cancer at the single-cell level\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/08\/29\/spatiotemporal-immune-landscape-and-long-term-immune-memory-in-pole-mutant-endometrial-cancer-at-the-single-cell-level\/\" aria-label=\"Read more about Spatiotemporal immune landscape and long-term immune memory in POLE-mutant endometrial cancer at the single-cell level\">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-41769","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\/41769","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=41769"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/41769\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=41769"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=41769"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=41769"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}