Inactivation of Interferon Receptor Promotes the Establishment of Immune Privileged Tumor Microenvironment.
Cancer Cell
; 31(2): 194-207, 2017 02 13.
Article
en En
| MEDLINE
| ID: mdl-28196594
ABSTRACT
Refractoriness of solid tumors, including colorectal cancers (CRCs), to immunotherapies is attributed to the immunosuppressive tumor microenvironment that protects malignant cells from cytotoxic T lymphocytes (CTLs). We found that downregulation of the type I interferon receptor chain IFNAR1 occurs in human CRC and mouse models of CRC. Downregulation of IFNAR1 in tumor stroma stimulated CRC development and growth, played a key role in formation of the immune-privileged niche, and predicted poor prognosis in human CRC patients. Genetic stabilization of IFNAR1 improved CTL survival and increased the efficacy of the chimeric antigen receptor T cell transfer and PD-1 inhibition. Likewise, pharmacologic stabilization of IFNAR1 suppressed tumor growth providing the rationale for upregulating IFNAR1 to improve anti-cancer therapies.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Receptor de Interferón alfa y beta
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Cell
Asunto de la revista:
NEOPLASIAS
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos