The immunogenomic landscape of resected intrahepatic cholangiocarcinoma.
Hepatology
; 75(2): 297-308, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-34510503
ABSTRACT
BACKGROUND AND AIMS:
Cholangiocarcinoma (CCA) is a deadly and highly therapy-refractory cancer of the bile ducts, with early results from immune checkpoint blockade trials showing limited responses. Whereas recent molecular assessments have made bulk characterizations of immune profiles and their genomic correlates, spatial assessments may reveal actionable insights. APPROACH ANDRESULTS:
Here, we have integrated immune checkpoint-directed immunohistochemistry with next-generation sequencing of resected intrahepatic CCA samples from 96 patients. We found that both T-cell and immune checkpoint markers are enriched at the tumor margins compared to the tumor center. Using two approaches, we identify high programmed cell death protein 1 or lymphocyte-activation gene 3 and low CD3/CD4/inducible T-cell costimulator specifically in the tumor center as associated with poor survival. Moreover, loss-of-function BRCA1-associated protein-1 mutations are associated with and cause elevated expression of the immunosuppressive checkpoint marker, B7 homolog 4.CONCLUSIONS:
This study provides a foundation on which to rationally improve and tailor immunotherapy approaches for this difficult-to-treat disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias dos Ductos Biliares
/
Antígenos CD
/
Colangiocarcinoma
/
Receptor de Morte Celular Programada 1
Limite:
Aged80
Idioma:
En
Revista:
Hepatology
Ano de publicação:
2022
Tipo de documento:
Article