Exploring the longitudinal glioma microenvironment landscape uncovers reprogrammed pro-tumorigenic neutrophils in the bone marrow

Prerna Magod, Ignacio Mastandrea, Liat Rousso-Noori, Lilach Agemy, Guy Shapira, Noam Shomron, Dinorah Friedmann-Morvinski

Research output: Contribution to journalArticlepeer-review

Abstract

Recent multi-omics studies show different immune tumor microenvironment (TME) compositions in glioblastoma (GBM). However, temporal comprehensive knowledge of the TME from initiation of the disease remains sparse. We use Cre recombinase (Cre)-inducible lentiviral murine GBM models to compare the cellular evolution of the immune TME in tumors initiated from different oncogenic drivers. We show that neutrophils infiltrate early during tumor progression primarily in the mesenchymal GBM model. Depleting neutrophils in vivo at the onset of disease accelerates tumor growth and reduces the median overall survival time of mice. We show that, as a tumor progresses, bone marrow-derived neutrophils are skewed toward a phenotype associated with pro-tumorigenic processes. Our findings suggest that GBM can remotely regulate systemic myeloid differentiation in the bone marrow to generate neutrophils pre-committed to a tumor-supportive phenotype. This work reveals plasticity in the systemic immune host microenvironment, suggesting an additional point of intervention in GBM treatment.

Original languageEnglish
Article number109480
JournalCell Reports
Volume36
Issue number5
DOIs
StatePublished - 3 Aug 2021

Keywords

  • cancer stem cells
  • glioblastoma
  • mouse models of cancer
  • neutrophils
  • plasticity
  • systemic reprogramming
  • tumor microenvironment

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