{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:52:03Z","timestamp":1793407923411,"version":"4.5.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"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><jats:title>Background<\/jats:title><jats:p>Radiation therapy can modulate the tumor microenvironment (TME), influencing antitumor immune responses. This study compared the immunomodulatory effects of alpha-emitting (<jats:sup>225<\/jats:sup>Ac) and beta-emitting (<jats:sup>177<\/jats:sup>Lu) radiopharmaceutical therapies (RPT) using NM600 in murine prostate cancer models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed immunological changes in TRAMP-C1 and Myc-CaP tumor models treated with <jats:sup>225<\/jats:sup>Ac-NM600 or <jats:sup>177<\/jats:sup>Lu-NM600. Flow cytometry was used to profile immune cell populations, activation markers, and checkpoint molecules, while multiplex assays analyzed cytokine and chemokine expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In general, <jats:sup>225<\/jats:sup>Ac-NM600 elicited stronger immunomodulatory effects than <jats:sup>177<\/jats:sup>Lu-NM600, including cell line dependent increased CD8\/Treg ratios, activation of effector and memory T cells, and depletion of suppressive Tregs and MDSCs. The treatment elevated Th1 cytokines, pro-inflammatory chemokines, and checkpoint molecules like PD-1 on CD8+ T cells and PD-L1 on MDSCs, creating a more \u201chot\u201d TME.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Alpha-emitting <jats:sup>225<\/jats:sup>Ac-NM600 demonstrated superior ability to enhance antitumor immunity compared to beta-emitting <jats:sup>177<\/jats:sup>Lu-NM600. These findings support the use of <jats:sup>225<\/jats:sup>Ac-NM600 in combination with immunotherapies for advanced prostate cancer treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1563387","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T05:26:04Z","timestamp":1747891564000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Immunomodulatory effects of alpha vs beta radiopharmaceutical therapy in murine prostate cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Carolina A.","family":"Ferreira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemanth 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