Desmoplastic Tumor Microenvironment and Immunotherapy in Cholangiocarcinoma

Dan Høgdall, Monika Lewinska, Jesper B Andersen


Cholangiocarcinoma (CCA) is a dismal disease which often is diagnosed at a late stage where the tumor is locally advanced, metastatic, and, as a result, is associated with low resectability. The heterogeneity of this cancer type is a major reason why the majority of patients fail to respond to therapy, and surgery remains their only curative option. Among patients who undergo surgical intervention, such tumors typically recur in 50% of cases within 1year. Thus, CCA is among the most aggressive and chemoresistant malignancies. CCA is characterized by marked tumor reactive stroma, a fibrogenic connective tissue which surrounds and infiltrates the tumor epithelium. This desmoplastic environment presents a clinical challenge, limiting drug delivery and supporting the growth of the tumor mass. In this review we attempt to highlight key pathways involved in cell to cell communication between the tumor epithelium and stroma, the immune components, and opportunities for novel strategies to improve patient outcome.

Original languageEnglish
JournalTrends in cancer
Issue number3
Pages (from-to)239-255
Number of pages17
Publication statusPublished - Mar 2018


  • Animals
  • Bile Duct Neoplasms/immunology
  • Cholangiocarcinoma/immunology
  • Cytokines/immunology
  • Humans
  • Immunotherapy
  • Receptors, Notch/immunology
  • STAT3 Transcription Factor/immunology
  • Tumor Microenvironment


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