The GM-CSF-IRF5 signaling axis in eosinophils promotes antitumor immunity through activation of type 1 T cell responses.
J Exp Med
; 217(12)2020 12 07.
Article
em En
| MEDLINE
| ID: mdl-32970801
ABSTRACT
The depletion of eosinophils represents an efficient strategy to alleviate allergic asthma, but the consequences of prolonged eosinophil deficiency for human health remain poorly understood. We show here that the ablation of eosinophils severely compromises antitumor immunity in syngeneic and genetic models of colorectal cancer (CRC), which can be attributed to defective Th1 and CD8+ T cell responses. The specific loss of GM-CSF signaling or IRF5 expression in the eosinophil compartment phenocopies the loss of the entire lineage. GM-CSF activates IRF5 in vitro and in vivo and can be administered recombinantly to improve tumor immunity. IL-10 counterregulates IRF5 activation by GM-CSF. CRC patients whose tumors are infiltrated by large numbers of eosinophils also exhibit robust CD8 T cell infiltrates and have a better prognosis than patients with eosinophillow tumors. The combined results demonstrate a critical role of eosinophils in tumor control in CRC and introduce the GM-CSF-IRF5 axis as a critical driver of the antitumor activities of this versatile cell type.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Fator Estimulador de Colônias de Granulócitos e Macrófagos
/
Células Th1
/
Eosinófilos
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Fatores Reguladores de Interferon
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Imunidade
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Suíça