Major histocompatibility complex class I expression impacts on patient survival and type and density of immune cells in biliary tract cancer

Br J Cancer. 2015 Nov 3;113(9):1343-9. doi: 10.1038/bjc.2015.337. Epub 2015 Oct 13.

Abstract

Background: Biliary tract cancers (BTC) are rare malignant tumours with a poor prognosis. Previously, we have presented a detailed characterisation of the inflammatory infiltrate in BTC. Here, we analysed the impact of the expression of major histocompatibility complex class I (MHC I) on patient survival and the quantity, as well as the quality of tumour-infiltrating immune cell types in BTC.

Methods: MHC I expression was assessed semi-quantitatively in 334 BTC, including extrahepatic (n=129) and intrahepatic cholangiocarcinomas (n=146), as well as adenocarcinomas of the gallbladder (n=59). In addition, 71 high-grade biliary intraepithelial lesions (BilIN 3) were included. Results were correlated with data on antitumour inflammation and investigated with respect to their association with clinicopathological variables and patient survival.

Results: BTC showed a wide spectrum of different MHC I expression patterns ranging from complete negativity in some tumours to strong homogenous expression in others. In BilIN 3, significantly higher MHC I expression levels were seen compared to invasive tumours (P=0.004). Patients with strong tumoural MHC I expression had a significantly higher overall survival probability (median survival benefit: 8 months; P=0.006). MHC I expression strongly correlated with the number of tumour-infiltrating T-lymphocytes (CD4(+) and CD8(+)) and macrophages.

Conclusions: Differences of MHC I expression predict patient outcome and show correlations with specific components of the inflammatory infiltrate in BTC. These findings contribute to a better understanding of immune response and immune escape phenomena in cholangiocarcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biliary Tract / immunology*
  • Biliary Tract / pathology
  • Female
  • Gallbladder Neoplasms / immunology*
  • Gallbladder Neoplasms / mortality*
  • Gallbladder Neoplasms / pathology
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Prognosis

Substances

  • Histocompatibility Antigens Class I