Immuno-Radiotherapy Enhances Tumor Control and Induces Abscopal Responses in a Humanized Mouse Model

Immuno-Radiotherapy Enhances Tumor Control and Induces Abscopal Responses in a Humanized Mouse Model | 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 Immuno-Radiotherapy Enhances Tumor Control and Induces Abscopal Responses in a Humanized Mouse Model Sébastien Penninckx, Morgane Cogels, Matteo Serra, Hugues Duvillier, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7188100/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Radiation therapy (RT) offers a tool to enhance immune checkpoint inhibitor (ICI) efficacy, yet its immunomodulatory potential remains poorly understood. Using a hematopoietic stem cell-humanized NOG mouse model bearing ICI-responsive renal cell carcinoma (RCC) or ICI-resistant non-small cell lung cancer (NSCLC) and melanoma, we reveal how RT dose-fractionation regimens shape local and systemic antitumor immunity. Immuno-RT (iRT) improved tumor control across models, and induced abscopal effects in ICI-resistant models, especially in NSCLC, where 3x8 Gy combined with ICI triggered systemic responses, increased circulating monocytes and remodeled the tumor microenvironment (TME). Flow cytometry, immunohistochemistry, and RNA-sequencing revealed dynamic immune remodeling, with late-stage responses in ICI-resistant tumors marked by low immune infiltration, high immune memory, cGAS/STING pathway, damage associated molecular patterns, cell death, and metabolic reprograming. Our findings support RT as a strategy to overcome ICI resistance and validate humanized mice as a translational model for iRT research. Biological sciences/Cancer/Cancer therapy/Radiotherapy Biological sciences/Cancer/Cancer therapy/Cancer immunotherapy Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Posted 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-7188100","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":491927984,"identity":"69ef2ff3-9dfc-4803-af73-6b9cb4197f98","order_by":0,"name":"Sébastien 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