Calnexin-TREM1 engagement improves tumor antigen presentation and enhances the activation of anti-tumor T cells

Calnexin-TREM1 engagement improves tumor antigen presentation and enhances the activation of anti-tumor T cells | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Calnexin-TREM1 engagement improves tumor antigen presentation and enhances the activation of anti-tumor T cells Nien-Jung Chen, Chien-Jung Li, Fu-Chen Yang, Yu-Wei Li, Kate Hua, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8016030/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Tumor-associated macrophages (TAMs) are associated with immunosuppression, but accumulating studies indicate they can support antitumor responses when reprogrammed. Here we identify TREM1, a myeloid immunoreceptor traditionally linked to inflammation, as a positive regulator of tumor antigen presentation. We also show that Calnexin is an agonistic ligand for TREM1 in the tumor microenvironment (TME). Using a recombinant Calnexin-based ligand called Tetra-CNX, we demonstrate that engagement of TREM1 reprograms TAMs into antigen-presenting cells that support cytotoxic and helper T cell responses, in part through a SYK-dependent program that enhances antigen processing and promotes MHC-I- and MHC-II–mediated T cell priming. This pathway is associated with a reduction in exhausted CD8⁺ T cells within the TME, suggesting improved anti-tumor T cell function. Our findings reposition TREM1 as a noncanonical modulator of adaptive immunity and highlight the therapeutic potential of engineered ligand-based strategies to restore myeloid cell function and enhance tumor-specific T cell responses. Biological sciences/Immunology/Tumour immunology/Immunosurveillance/Immunoediting Biological sciences/Immunology/Antigen processing and presentation/Antigen-presenting cells Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8016030","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":541459085,"identity":"928be27b-752e-4f85-b8b5-6273503faaa1","order_by":0,"name":"Nien-Jung 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