{"id":36162,"date":"2025-06-25T18:50:09","date_gmt":"2025-06-25T16:50:09","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/06\/25\/nc410-a-bivalent-lair-2-construct-remodels-collagen-in-the-tumor-microenvironment-and-abrogates-neutrophil-driven-t-cell-suppression\/"},"modified":"2025-06-25T18:50:09","modified_gmt":"2025-06-25T16:50:09","slug":"nc410-a-bivalent-lair-2-construct-remodels-collagen-in-the-tumor-microenvironment-and-abrogates-neutrophil-driven-t-cell-suppression","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/06\/25\/nc410-a-bivalent-lair-2-construct-remodels-collagen-in-the-tumor-microenvironment-and-abrogates-neutrophil-driven-t-cell-suppression\/","title":{"rendered":"NC410, a bivalent LAIR-2 construct, remodels collagen in the tumor microenvironment and abrogates neutrophil-driven T cell suppression"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Jun 25:vkaf121. doi: 10.1093\/jimmun\/vkaf121. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>We previously observed that circulating human neutrophils exposed to epithelial ovarian cancer (OC) ascites fluid supernatants (ASC) and malignant effusions from other tumors acquire T cell suppressor function. Collagen motifs ligate LAIR-1, an inhibitory SHP-1-dependent checkpoint broadly expressed on immune cells. We hypothesized that NC410, a bivalent LAIR-2 construct that inhibits LAIR-1-collagen binding, would rescue neutrophil-driven T cell non-responsiveness. NC410 remodeled ASC collagen resulting in neutrophil clustering and reduction in neutrophil-T cell contact, abrogated ASC-induced neutrophil trogocytosis of T cell membranes and rescued stimulated T cell proliferation. Mean ASC pro-collagen-1\u03b1 levels were &gt;100-fold greater than serum samples. In a single-center retrospective analysis, after adjusting for age, stage and optimal debulking, ASC pro-collagen-1\u03b1 and serum sLAIR-1 levels were each associated with worse overall survival (OS), and ASC LAIR-2 levels were associated with better OS. Multispectral imaging of high-grade serous ovarian cancer and non-small cell lung cancer showed highly variable LAIR-1 staining in both tumor cell and immune infiltrates. The proportion of collagen-1-positive cells was highest among tumor cells and tumor-infiltrating immune cells versus stromal immune cells, raising the potential role of tumor-associated collagen limiting immune cell infiltration into tumor. Our results support further evaluation of circulating and tumor-associated collagen products and LAIR-1 and LAIR-2 as prognostic biomarkers in advanced OC and as biomarkers for clinical response to NC410 and to other collagen- and LAIR-directed therapies.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40560129\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250625125008&amp;v=2.18.0.post9+e462414\">40560129<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf121\">10.1093\/jimmun\/vkaf121<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Jun 25:vkaf121. doi: 10.1093\/jimmun\/vkaf121. Online ahead of print. ABSTRACT We previously observed that circulating human neutrophils exposed to epithelial ovarian cancer (OC) ascites fluid supernatants (ASC) and malignant effusions from other tumors acquire T cell suppressor function. Collagen motifs ligate LAIR-1, an inhibitory SHP-1-dependent checkpoint broadly expressed on immune cells. We hypothesized &#8230; <a title=\"NC410, a bivalent LAIR-2 construct, remodels collagen in the tumor microenvironment and abrogates neutrophil-driven T cell suppression\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/06\/25\/nc410-a-bivalent-lair-2-construct-remodels-collagen-in-the-tumor-microenvironment-and-abrogates-neutrophil-driven-t-cell-suppression\/\" aria-label=\"Read more about NC410, a bivalent LAIR-2 construct, remodels collagen in the tumor microenvironment and abrogates neutrophil-driven T cell suppression\">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":[42,71],"tags":[],"class_list":["post-36162","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/36162","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=36162"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/36162\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=36162"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=36162"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=36162"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}