Nature genetics · 2026
Childhood brain tumors instruct cranial hematopoiesis and immunotolerance.
СтатьяПоддержка исследования: вне правительства СШАНазвание 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.
Cooper Elizabeth, Posner David A, Lee Colin Y C, Hu Linda, Bonner Sigourney, Taylor Jessica T, Baldwin Oscar, Jimenez-Guerrero Rocio, Masih Katherine E, Rahrmann Katherine Wickham, Eigenbrood Jason, Ngo Gina, Franklin Valar Nila Roamio, D'Santos Clive S, Mair Richard, Santarius Thomas, Craven Claudia, Jalloh Ibrahim, Moreno Vicente Julia, Halim Timotheus Y F, Wang Li, Kreigstien Arnold R, Wainwright Brandon, Swartling Fredrik J, Khan Javed, Clatworthy Menna R, Gilbertson Richard J
Аннотация
Recent research has challenged a long-held view of the brain as an immune-privileged organ, revealing active immunosurveillance with therapeutic relevance. Using a new genetically engineered mouse model of ZFTA-RELA ependymoma, a childhood brain tumor, we characterized an immune circuit between the tumor and antigen-presenting hematopoietic stem and progenitor cells (HSPCs) in the skull bone marrow. The presentation of antigens by HSPCs to CD4+ T cells biased HSPC lineages toward myelopoiesis and polarized CD4+ T cells to regulatory T cells, culminating in tumor immunotolerance. Remarkably, normalizing hematopoiesis with a single infusion of antibodies directed against cytokines enriched in the cerebrospinal fluid of mice bearing ZFTA-RELA ependymomas, choroid plexus carcinomas or group 3 medulloblastoma-all aggressive childhood brain tumors-disrupted this process and caused profound tumor regression. These findings demonstrate the existence of a skull bone marrow-tumor immunological interface and suggest that modulating the local supply of myeloid cells could represent a less toxic therapeutic strategy for aggressive childhood brain tumors.