Glioblastoma induces the recruitment and differentiation of dendritic-like “hybrid” neutrophils from skull bone marrow

Tumor-associated neutrophil (TAN) effects on glioblastoma (GBM) biology remain under-characterized. We show here that neutrophils with dendritic features—including morphological complexity, expression of antigen presentation genes, and the ability to process exogenous peptide and stimulate major his...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cancer cell 2024-09, Vol.42 (9), p.1549-1569.e16
Hauptverfasser: Lad, Meeki, Beniwal, Angad S., Jain, Saket, Shukla, Poojan, Kalistratova, Venina, Jung, Jangham, Shah, Sumedh S., Yagnik, Garima, Saha, Atul, Sati, Ankita, Babikir, Husam, Nguyen, Alan T., Gill, Sabraj, Rios, Jennifer, Young, Jacob S., Lui, Austin, Salha, Diana, Diaz, Aaron, Aghi, Manish K.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Tumor-associated neutrophil (TAN) effects on glioblastoma (GBM) biology remain under-characterized. We show here that neutrophils with dendritic features—including morphological complexity, expression of antigen presentation genes, and the ability to process exogenous peptide and stimulate major histocompatibility complex (MHC)II-dependent T cell activation—accumulate intratumorally and suppress tumor growth in vivo. Trajectory analysis of patient TAN scRNA-seq identifies this “hybrid” dendritic-neutrophil phenotype as a polarization state that is distinct from canonical cytotoxic TANs, and which differentiates from local precursors. These hybrid-inducible immature neutrophils—which we identified in patient and murine glioblastomas—arise not from circulation, but from local skull marrow. Through labeled skull flap transplantation and targeted ablation, we characterize calvarial marrow as a contributor of antitumoral myeloid antigen-presenting cells (APCs), including TANs, which elicit T cell cytotoxicity and memory. As such, agents augmenting neutrophil egress from skull marrow—such as intracalvarial AMD3100, whose survival-prolonging effect in GBM we report—present therapeutic potential. [Display omitted] •“Hybrid” dendritic-neutrophils in GBM activate T cells in an MHCII-dependent manner•Neutrophil suppression of GBM growth depends on T cells and involves IFN signaling•Hybrid differentiation occurs intratumorally from precursors rarely seen in blood•Skull marrow contributes immature and antigen-presenting myeloid cells to GBM Lad et al. demonstrate that calvarial bone marrow supplies the glioblastoma microenvironment with antigen-presenting myeloid cells, including immature neutrophils that polarize into a “hybrid” dendritic-like phenotype. These findings convey the skull marrow as a physiologically relevant and thus clinically targetable immune component of CNS malignancies.
ISSN:1535-6108
1878-3686
1878-3686
DOI:10.1016/j.ccell.2024.08.008