{"id":62623,"date":"2026-04-24T19:01:28","date_gmt":"2026-04-24T17:01:28","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/04\/24\/nmb-cxcl13-cd4-t-cells-derived-neuromedin-b-promotes-neuropeptide-s-receptor-1-positive-malignant-cells-senescence-and-malignancy\/"},"modified":"2026-04-24T19:01:28","modified_gmt":"2026-04-24T17:01:28","slug":"nmb-cxcl13-cd4-t-cells-derived-neuromedin-b-promotes-neuropeptide-s-receptor-1-positive-malignant-cells-senescence-and-malignancy","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/04\/24\/nmb-cxcl13-cd4-t-cells-derived-neuromedin-b-promotes-neuropeptide-s-receptor-1-positive-malignant-cells-senescence-and-malignancy\/","title":{"rendered":"NMB+ CXCL13+ CD4+ T cells -derived neuromedin-B promotes neuropeptide S receptor 1 positive malignant cells senescence and malignancy"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 Apr 24. doi: 10.1158\/2326-6066.CIR-25-1081. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Colorectal cancer (CRC) with liver metastases (CRCLM) remains a clinical challenge. CXCL13 is widely recognized as a biomarker of immunotherapy response. However, the functional heterogeneity (protumor vs. antitumor) of CXCL13\u207aCD4\u207a T cell subsets has long been controversial. Through integrated analysis of single-cell RNA sequencing data from CRC clinical samples and pan-cancer datasets, combined with experimental validations, we first identified a pro-metastatic NMB\u207aCXCL13\u207aCD4\u207a T cell subset and uncovered a mechanism by which this subset regulates tumor cell &#8220;senescence-malignant transition&#8221;, the NMB-NPSR1 axis. These NMB\u207aCXCL13\u207aCD4\u207a T cells induced senescence in NPSR1\u207a malignant cells via NMB secretion, leading to enhanced invasiveness and migration despite reduced proliferation. Activation of NPSR1 triggered the Wnt signaling pathway and Epithelial-Mesenchymal Transition (EMT), thereby enhancing cellular malignancy. This NPSR1+ senescent subpopulation also recruited endothelial cells and disrupted tight junction integrity, fostering a pro-metastatic microenvironment. As a proof-of-principle study, combination of the NPSR1 inhibitor SHA68 and anti-PD1 demonstrated remarkable antitumor effects using mouse models of CRC metastasis. Overall, this study uncovered the role of NMB+ CXCL13+ CD4+ T cells in promoting tumor cell senescence while influencing tumor metastasis, offering potential clinical implications for the diagnosis and treatment of metastatic CRC.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42029557\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260424130128&amp;v=2.19.0.post6+133c1fe\">42029557<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-1081\">10.1158\/2326-6066.CIR-25-1081<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 Apr 24. doi: 10.1158\/2326-6066.CIR-25-1081. Online ahead of print. ABSTRACT Colorectal cancer (CRC) with liver metastases (CRCLM) remains a clinical challenge. CXCL13 is widely recognized as a biomarker of immunotherapy response. However, the functional heterogeneity (protumor vs. antitumor) of CXCL13\u207aCD4\u207a T cell subsets has long been controversial. Through integrated analysis of single-cell &#8230; <a title=\"NMB+ CXCL13+ CD4+ T cells -derived neuromedin-B promotes neuropeptide S receptor 1 positive malignant cells senescence and malignancy\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/04\/24\/nmb-cxcl13-cd4-t-cells-derived-neuromedin-b-promotes-neuropeptide-s-receptor-1-positive-malignant-cells-senescence-and-malignancy\/\" aria-label=\"Read more about NMB+ CXCL13+ CD4+ T cells -derived neuromedin-B promotes neuropeptide S receptor 1 positive malignant cells senescence and malignancy\">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-62623","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\/62623","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=62623"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/62623\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=62623"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=62623"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=62623"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}