{"id":21179,"date":"2025-01-02T19:46:01","date_gmt":"2025-01-02T18:46:01","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/01\/02\/spatial-organization-of-macrophages-in-ctl-rich-hepatocellular-carcinoma-influences-ctl-antitumor-activity\/"},"modified":"2025-01-02T19:46:01","modified_gmt":"2025-01-02T18:46:01","slug":"spatial-organization-of-macrophages-in-ctl-rich-hepatocellular-carcinoma-influences-ctl-antitumor-activity","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/01\/02\/spatial-organization-of-macrophages-in-ctl-rich-hepatocellular-carcinoma-influences-ctl-antitumor-activity\/","title":{"rendered":"Spatial Organization of Macrophages in CTL Rich Hepatocellular Carcinoma Influences CTL Antitumor Activity"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Jan 2. doi: 10.1158\/2326-6066.CIR-24-0589. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Despite the pivotal role of cytotoxic T lymphocytes (CTLs) in anti-tumor immunity, a substantial proportion of CTL-rich hepatocellular carcinoma (HCC) patients experience early relapse or immunotherapy resistance. However, spatial immune variations impacting the heterogeneous clinical outcomes of CTL-rich HCCs remain poorly understood. Here, we compared the single-cell and spatial landscapes of 20 CTL-rich HCCs with distinct prognoses using multiplexed in situ staining and validated the prognostic value of myeloid spatial patterns in a cohort of 386 patients. Random forest and Cox regression models identified macrophage aggregation as a distinctive spatial pattern characterizing a subset of CTL-rich HCCs with an immunosuppressive microenvironment and poor prognosis. Integrated analysis of single-cell and spatial transcriptomics, combined with in situ staining validation, revealed that spatial aggregation enhanced pro-tumoral macrophage reprogramming in HCCs, marked by lipid metabolism orientation, M2-like polarization, and increased adjacent CTL exhaustion. This spatial effect on macrophage reprogramming was replicated in HCC-conditioned human macrophage cultures, which showed an enhanced capability to suppress CTLs. Notably, increased macrophage aggregation was associated with higher response rates to anti-PD-1 immunotherapy. These findings suggest that the spatial distribution of macrophages is a biomarker of their functional diversities and microenvironment status, which holds prognostic and therapeutic implications.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39745778\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250102134600&amp;v=2.18.0.post9+e462414\">39745778<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-0589\">10.1158\/2326-6066.CIR-24-0589<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Jan 2. doi: 10.1158\/2326-6066.CIR-24-0589. Online ahead of print. ABSTRACT Despite the pivotal role of cytotoxic T lymphocytes (CTLs) in anti-tumor immunity, a substantial proportion of CTL-rich hepatocellular carcinoma (HCC) patients experience early relapse or immunotherapy resistance. However, spatial immune variations impacting the heterogeneous clinical outcomes of CTL-rich HCCs remain poorly understood. &#8230; <a title=\"Spatial Organization of Macrophages in CTL Rich Hepatocellular Carcinoma Influences CTL Antitumor Activity\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/01\/02\/spatial-organization-of-macrophages-in-ctl-rich-hepatocellular-carcinoma-influences-ctl-antitumor-activity\/\" aria-label=\"Read more about Spatial Organization of Macrophages in CTL Rich Hepatocellular Carcinoma Influences CTL Antitumor Activity\">Read more<\/a><\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-21179","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\/21179","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"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=21179"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/21179\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=21179"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=21179"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=21179"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}