The immunogenomic landscape of resected intrahepatic cholangiocarcinoma

Fernando Carapeto, Behnaz Bozorgui, Rachna T. Shroff, Sharmeen Chagani, Luisa Solis Soto, Wai Chin Foo, Ignacio Wistuba, Funda Meric-Bernstam, Ahmed Shalaby, Milind Javle, Anil Korkut, Lawrence N. Kwong

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)297-308
Number of pages12
JournalHepatology
Volume75
Issue number2
DOIs
StatePublished - Feb 2022

ASJC Scopus subject areas

  • Hepatology

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