Oncolytic Virus-Mediated Targeting of PGE2 in the Tumor Alters the Immune Status and Sensitizes Established and Resistant Tumors to Immunotherapy.
Cancer Cell
; 30(1): 108-119, 2016 07 11.
Article
em En
| MEDLINE
| ID: mdl-27374223
ABSTRACT
Immunotherapies are highly promising cancer treatments, but understanding the factors mediating their resistance remains critical. Successes in randomized clinical testing have supported the growing appreciation that oncolytic virotherapies primarily act as immunotherapies. Here we identified prostaglandin E2 (PGE2) in the tumor as a key mediator of resistance to immunotherapies, including oncolytic vaccinia virotherapy. Elevated levels of PGE2 coupled to suppressive chemokine profiles and high levels of granulocytic myeloid-derived suppressor cells resulted in loss of immunotherapeutic potential. Viral vectors engineered to target PGE2 were capable of overcoming localized immunosuppression leading to profound changes in the tumor's immune status. This allowed the viral vectors to raise robust anti-tumor adaptive immune responses and sensitized established and previously resistant tumors to immunotherapies.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dinoprostona
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Hidroxiprostaglandina Desidrogenases
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Marcação de Genes
/
Quimiocinas
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Terapia Viral Oncolítica
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Neoplasias Experimentais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos