{"id":46869,"date":"2025-10-27T23:51:21","date_gmt":"2025-10-27T22:51:21","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/10\/27\/downregulation-of-hla-class-i-expression-through-hla-a-dna-methylation-is-associated-with-reduced-cd8-t-cell-infiltration-in-cervical-cancer\/"},"modified":"2025-10-27T23:51:21","modified_gmt":"2025-10-27T22:51:21","slug":"downregulation-of-hla-class-i-expression-through-hla-a-dna-methylation-is-associated-with-reduced-cd8-t-cell-infiltration-in-cervical-cancer","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/10\/27\/downregulation-of-hla-class-i-expression-through-hla-a-dna-methylation-is-associated-with-reduced-cd8-t-cell-infiltration-in-cervical-cancer\/","title":{"rendered":"Downregulation of HLA Class I Expression Through HLA-A DNA Methylation Is Associated with Reduced CD8+ T Cell Infiltration in Cervical Cancer"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Oct 27. doi: 10.1158\/2326-6066.CIR-25-0594. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Human leukocyte antigen class I (HLA-I) is central to tumor immune recognition, but its regulatory mechanisms in cervical cancer remain poorly understood. This study aimed to elucidate the impact of HLA-I regulatory mechanisms on CD8+ T cell infiltration and identify distinct histotype-specific immune escape strategies across cervical cancer subtypes. Using 98 cervical cancer cases, including squamous cell carcinoma (SCC, n=53), adenocarcinoma (AC, n=32), gastric-type adenocarcinoma (GAS, n=5), small cell carcinoma (Small, n=4), and mixed histological types (MIX, n=4), we examined the relationship between CD8+ T cell infiltration patterns (categorized as Infiltrated, Excluded, or Absent) and HLA-I expression, HLA-A DNA methylation, and HLA-I loss of heterozygosity (LOH). CD8+ T cell infiltration patterns varied significantly by histological subtype (P&lt;0.0001). SCC showed the highest frequency of the Infiltrated pattern (73.6%), whereas GAS and Small predominantly displayed an Absent pattern. Reduced CD8+ T cell infiltration correlated with poor survival (P&lt;0.0001). HLA-I expression mirrored these trends, being highest in SCC and lowest in Small and GAS. HLA-A DNA methylation emerged as a key driver of HLA-I downregulation, leading to reduced CD8+ infiltration (P&lt;0.05). In SCC, both HLA-A methylation and HLA-I LOH contributed to immune evasion; cases lacking these alterations exhibited the highest CD8+ T cell infiltration levels (P&lt;0.01). This study identifies distinct HLA-I regulatory mechanisms in cervical cancer, highlighting HLA-A methylation-and particularly HLA-I LOH in SCC-as key drivers of immune evasion. These findings provide a foundation for developing predictive biomarkers and suggest that targeting these specific HLA-I regulatory mechanisms could enhance immunotherapy efficacy.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41144789\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20251027185120&amp;v=2.18.0.post22+67771e2\">41144789<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-0594\">10.1158\/2326-6066.CIR-25-0594<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Oct 27. doi: 10.1158\/2326-6066.CIR-25-0594. Online ahead of print. ABSTRACT Human leukocyte antigen class I (HLA-I) is central to tumor immune recognition, but its regulatory mechanisms in cervical cancer remain poorly understood. This study aimed to elucidate the impact of HLA-I regulatory mechanisms on CD8+ T cell infiltration and identify distinct histotype-specific &#8230; <a title=\"Downregulation of HLA Class I Expression Through HLA-A DNA Methylation Is Associated with Reduced CD8+ T Cell Infiltration in Cervical Cancer\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/10\/27\/downregulation-of-hla-class-i-expression-through-hla-a-dna-methylation-is-associated-with-reduced-cd8-t-cell-infiltration-in-cervical-cancer\/\" aria-label=\"Read more about Downregulation of HLA Class I Expression Through HLA-A DNA Methylation Is Associated with Reduced CD8+ T Cell Infiltration in Cervical 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":[55,42],"tags":[],"class_list":["post-46869","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\/46869","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=46869"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/46869\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=46869"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=46869"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=46869"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}