Immunobiology of cholangiocarcinoma

Emilien Loeuillard, Caitlin B. Conboy, Gregory J. Gores, Sumera Rizvi

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations

Abstract

Cholangiocarcinoma (CCA) represents a heterogeneous group of epithelial tumours that are classified according to anatomical location as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA). Although surgical resection and liver transplantation following neoadjuvant therapy are potentially curative options for a subset of patients with early-stage disease, the currently available medical therapies for CCA have limited efficacy. Immunotherapeutic strategies such as immune checkpoint blockade (ICB) harness the host immune system to unleash an effective and durable antitumour response in a subset of patients with a variety of malignancies. However, response to ICB monotherapy has been relatively disappointing in CCA. CCAs are desmoplastic tumours with an abundant tumour immune microenvironment (TIME) that contains immunosuppressive innate immune cells such as tumour-associated macrophages and myeloid-derived suppressor cells. A subset of CCAs may be classified as immune ‘hot’ tumours with a high density of CD8+ T cells and enhanced expression of immune checkpoint molecules. Immune ‘hot’ tumour types are associated with higher response rates to ICB. However, the suboptimal response rates to ICB monotherapy in human clinical trials of CCA imply that the preponderance of CCAs are immune ‘cold’ tumours with a non-T cell infiltrated TIME. An enhanced comprehension of the immunobiology of CCA, particularly the innate immune response to CCA, is essential in the effort to develop effective combination immunotherapeutic strategies that can target a larger subset of CCAs.

Original languageEnglish (US)
Pages (from-to)297-311
Number of pages15
JournalJHEP Reports
Volume1
Issue number4
DOIs
StatePublished - Oct 2019

Keywords

  • Distal cholangiocarcinoma
  • immune checkpoint blockade
  • immune cold CCA
  • immune hot CCA
  • intrahepatic cholangiocarcinoma
  • perihilar cholangiocarcinoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Internal Medicine
  • Hepatology
  • Gastroenterology

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