GADD45ß Loss Ablates Innate Immunosuppression in Cancer.
Cancer Res
; 78(5): 1275-1292, 2018 03 01.
Article
en En
| MEDLINE
| ID: mdl-29279355
ABSTRACT
T-cell exclusion from the tumor microenvironment (TME) is a major barrier to overcoming immune escape. Here, we identify a myeloid-intrinsic mechanism governed by the NF-κB effector molecule GADD45ß that restricts tumor-associated inflammation and T-cell trafficking into tumors. In various models of solid cancers refractory to immunotherapies, including hepatocellular carcinoma and ovarian adenocarcinoma, Gadd45b inhibition in myeloid cells restored activation of proinflammatory tumor-associated macrophages (TAM) and intratumoral immune infiltration, thereby diminishing oncogenesis. Our results provide a basis to interpret clinical evidence that elevated expression of GADD45B confers poor clinical outcomes in most human cancers. Furthermore, they suggest a therapeutic target in GADD45ß for reprogramming TAM to overcome immunosuppression and T-cell exclusion from the TME.Significance:
These findings define a myeloid-based immune checkpoint that restricts T-cell trafficking into tumors, with potentially important therapeutic implications to generally improve the efficacy of cancer immunotherapy. Cancer Res; 78(5); 1275-92. ©2017 AACR.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Antígenos de Diferenciación
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Terapia de Inmunosupresión
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Carcinoma Hepatocelular
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Microambiente Tumoral
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Tolerancia Inmunológica
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Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Cancer Res
Año:
2018
Tipo del documento:
Article
País de afiliación:
Italia