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<p>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 <i>ZFTA</i><i>–RELA</i> 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<sup>+</sup> T cells biased HSPC lineages toward myelopoiesis and polarized CD4<sup>+</sup> 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 <i>ZFTA</i><i>–RELA</i> 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.</p>

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Childhood brain tumors instruct cranial hematopoiesis and immunotolerance

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月3日

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  • Elizabeth Cooper,
  • David A. Posner,
  • Colin Y. C. Lee,
  • Linda Hu,
  • Sigourney Bonner,
  • Jessica T. Taylor,
  • Oscar Baldwin,
  • Rocio Jimenez-Guerrero,
  • Katherine E. Masih,
  • Katherine Wickham Rahrmann,
  • Jason Eigenbrood,
  • Gina Ngo,
  • Valar Nila Roamio Franklin,
  • Clive S. D’Santos,
  • Richard Mair,
  • Thomas Santarius,
  • Claudia Craven,
  • Ibrahim Jalloh,
  • Julia Moreno Vicente,
  • Timotheus Y. F. Halim,
  • Li Wang,
  • Arnold R. Kreigstien,
  • Brandon Wainwright,
  • Fredrik J. Swartling,
  • Javed Khan,
  • Menna R. Clatworthy,
  • Richard J. Gilbertson

摘要

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.