Ependymoma instructs cranial haematopoiesis and immunotolerance

ABSTRACT: ZFTA-RELA ependymoma presents a significant clinical challenge due to the lack of effective treatments, driving the need to explore novel immunotherapeutic strategies. Recent studies have identified the skull bone marrow as a source of meningeal immune cells critical for central nervous system (CNS) immunity, yet the role of these cells in childhood CNS tumour surveillance and pathology remains unclear. Here, we demonstrate that intracranial childhood ependymoma tumours harbour a unique myeloid cell population, including hematopoietic stem cells (HSCs) not from the blood, but supplied by adjacent skull bone marrow, ontogenetically distinct from their blood-derived counterparts. Our findings challenge the conventional view of HSCs as passive players in the CNS, revealing that antigen-specific interactions between skull bone marrow-derived HSCs and CD4+ T cells actively promote immunotolerance in childhood brain tumours by enhancing local myelopoiesis and inducing regulatory T cell polarization. This work uncovers a previously unrecognized cellular network linking the skull to brain tumours in children and underscores the therapeutic potential of modulating skull bone marrow haematopoiesis to shift the local immune environment. Targeting this skull-specific immune pathway offers a promising avenue for developing localized immunotherapies to improve treatment outcomes.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cerebrospinal Fluid Secretion, Cerebrospinal Fluid

DISEASE(S): Brain Cancer

SUBMITTER: Valar Nila Roamio Franklin  

LAB HEAD: Clive D'Santos

PROVIDER: PXD058239 | Pride | 2025-12-01

REPOSITORIES: Pride