{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T22:37:46Z","timestamp":1773268666060,"version":"3.50.1"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Radiation therapy (RT) offers a tool to enhance immune checkpoint inhibitor (ICI) efficacy, yet its immunomodulatory potential remains poorly understood. Here, we investigated how RT dose-fractionation regimens shape local and systemic antitumor immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A hematopoietic stem cell-humanized NOG mouse model was established, bearing ICI-responsive renal cell carcinoma (RCC) or ICI-resistant non-small cell lung cancer (NSCLC) and melanoma. Mice were treated with RT using different dose-fractionation regimens in combination with ICI. Tumor growth, systemic immune responses, and abscopal effects were assessed. Immune remodeling was characterized by flow cytometry, immunohistochemistry, and RNA-sequencing analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results &amp;amp; discussion<\/jats:title>\n                    <jats:p>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). Late-stage responses in ICI-resistant tumors were marked by low immune infiltration but enriched signatures of immune memory, cGAS\/STING pathway, damage associated molecular patterns, cell death, and metabolic reprogramming. Our findings support RT as a strategy to overcome ICI resistance and validate humanized mice as a translational model for iRT research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1774955","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T06:50:49Z","timestamp":1773211849000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immuno-radiotherapy enhances tumor control and induces abscopal responses in a humanized mouse model"],"prefix":"10.3389","volume":"17","author":[{"given":"Morgane M.","family":"Cogels","sequence":"first","affiliation":[{"name":"Department of Radiotherapy, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (HUB)","place":["Brussels, Belgium"]},{"name":"Radiophysics Laboratory, Universit\u00e9 Libre de Bruxelles (ULB), Faculty of Medicine","place":["Brussels, Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Serra","sequence":"additional","affiliation":[{"name":"Breast Cancer Translational Research Laboratory J.-C. 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