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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 &amp;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.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf121","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T10:24:10Z","timestamp":1750847050000},"page":"2464-2479","source":"Crossref","is-referenced-by-count":2,"title":["NC410, a bivalent LAIR-2 construct, remodels collagen in the tumor microenvironment and abrogates neutrophil-driven T cell suppression"],"prefix":"10.1093","volume":"214","author":[{"given":"Thejaswini","family":"Giridharan","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Michigan , Ann Arbor, MI,","place":["United 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