Key role for neutrophils in radiation-induced antitumor immune responses: Potentiation with G-CSF.
Proc Natl Acad Sci U S A
; 113(40): 11300-11305, 2016 10 04.
Article
em En
| MEDLINE
| ID: mdl-27651484
ABSTRACT
Radiation therapy (RT), a major modality for treating localized tumors, can induce tumor regression outside the radiation field through an abscopal effect that is thought to involve the immune system. Our studies were designed to understand the early immunological effects of RT in the tumor microenvironment using several syngeneic mouse tumor models. We observed that RT induced sterile inflammation with a rapid and transient infiltration of CD11b+Gr-1high+ neutrophils into the tumors. RT-recruited tumor-associated neutrophils (RT-Ns) exhibited an increased production of reactive oxygen species and induced apoptosis of tumor cells. Tumor infiltration of RT-Ns resulted in sterile inflammation and, eventually, the activation of tumor-specific cytotoxic T cells, their recruitment into the tumor site, and tumor regression. Finally, the concurrent administration of granulocyte colony-stimulating factor (G-CSF) enhanced RT-mediated antitumor activity by activating RT-Ns. Our results suggest that the combination of RT and G-CSF should be further evaluated in preclinical and clinical settings.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator Estimulador de Colônias de Granulócitos
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Neoplasias
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Neutrófilos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article