Aims
Cholangiocarcinoma (CCA) is a deadly and highly therapy-refractory cancer of the bile ducts, with early
Approach and results
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.
Background and aims
Cholangiocarcinoma (CCA) is a deadly and highly therapy-refractory cancer of the bile ducts, with early
Conclusions
This study provides a foundation on which to rationally improve and tailor immunotherapy approaches for this difficult-to-treat disease.
Results
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.