Frontiers in immunology · 2025
Immunomodulatory effects of alpha vs beta radiopharmaceutical therapy in murine prostate cancer.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ferreira Carolina A, Potluri Hemanth K, Mahmoudian Mojdeh, Massey Christopher F, Grudzinski Joseph J, Carston Amanda M, Clemons Nathan B, Idrissou Malick Bio, Thickens Anna S, Rosenkrans Zachary T, Choi Cynthia, Kerr Caroline P, Pinchuk Anatoly N, Kwon Ohyun, Jeffery Justin J, Bednarz Bryan P, Morris Zachary S, Weichert Jamey P, McNeel Douglas G, Hernandez Reinier
Аннотация
BACKGROUND: Radiation therapy can modulate the tumor microenvironment (TME), influencing antitumor immune responses. This study compared the immunomodulatory effects of alpha-emitting (225Ac) and beta-emitting (177Lu) radiopharmaceutical therapies (RPT) using NM600 in murine prostate cancer models.
METHODS: We assessed immunological changes in TRAMP-C1 and Myc-CaP tumor models treated with 225Ac-NM600 or 177Lu-NM600. Flow cytometry was used to profile immune cell populations, activation markers, and checkpoint molecules, while multiplex assays analyzed cytokine and chemokine expression.
RESULTS: In general, 225Ac-NM600 elicited stronger immunomodulatory effects than 177Lu-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 "hot" TME.
CONCLUSION: Alpha-emitting 225Ac-NM600 demonstrated superior ability to enhance antitumor immunity compared to beta-emitting 177Lu-NM600. These findings support the use of 225Ac-NM600 in combination with immunotherapies for advanced prostate cancer treatment.
METHODS: We assessed immunological changes in TRAMP-C1 and Myc-CaP tumor models treated with 225Ac-NM600 or 177Lu-NM600. Flow cytometry was used to profile immune cell populations, activation markers, and checkpoint molecules, while multiplex assays analyzed cytokine and chemokine expression.
RESULTS: In general, 225Ac-NM600 elicited stronger immunomodulatory effects than 177Lu-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 "hot" TME.
CONCLUSION: Alpha-emitting 225Ac-NM600 demonstrated superior ability to enhance antitumor immunity compared to beta-emitting 177Lu-NM600. These findings support the use of 225Ac-NM600 in combination with immunotherapies for advanced prostate cancer treatment.