Immune Niche Formation Reveals Mechanisms of Tumor Dormancy and Targeting Opportunities

Immune Niche Formation Reveals Mechanisms of Tumor Dormancy and Targeting Opportunities | 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 Immune Niche Formation Reveals Mechanisms of Tumor Dormancy and Targeting Opportunities Li Yang, Abdul Ahad, Feng Leng, Hiroshi Ichise, Edward Schrom, and 15 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8167536/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 Residual tumor cells can persist in a dormant state during clinical remissions that may last decades. The mechanisms leading to such growth control vs. eventual macroscopic metastases remain unclear. Here, we report abrogation of myeloid TGF-β RII resulted in an IFN-γ rich microenvironment. IFN-γ in turn elevated KLF4-mediated SLURP1 production in malignant cells, which is critical to their quiescent state through interruption of fibronectin-integrin pathways. The dormant tumor lesions were found in spatially localized immune niches rich in NK cells, cDCs, monocytes, and neutrophils, concomitant with tumor cell inactivation of NK cell immune surveillance through CD200-CD200R1. Our studies identify the IFN-γ-KLF4-SLURP1 and CD200-CD200R1 axes as critical molecular drivers in tumor dormancy regulated by immune-tumor crosstalk. Targeting the CD200-mediated dormant niche in combination with chemotherapy and immune check point blockade (ICB) significantly eradicated the dormant tumor cells. These insights provide mechanistic understanding of tumor dormancy and treatment options for ICB relapse. Biological sciences/Cancer/Cancer microenvironment Biological sciences/Cancer/Cancer therapy/Cancer immunotherapy Tumor dormancy immune niche metastasis relapse TGF-β Full Text Additional Declarations There is NO Competing Interest. Supplementary Files supplefigures11222025bprintLY.pdf supple figure and table 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. 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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-8167536","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":551663737,"identity":"11d74619-c8ca-4c73-9c73-7708207dd33e","order_by":0,"name":"Li 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