Exploring the longitudinal glioma microenvironment landscape uncovers reprogrammed pro-tumorigenic neutrophils in the bone marrow.
Cell Rep
; 36(5): 109480, 2021 08 03.
Article
em En
| MEDLINE
| ID: mdl-34348160
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Medula Óssea
/
Neoplasias Encefálicas
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Microambiente Tumoral
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Carcinogênese
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Glioma
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Neutrófilos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article