Interaction of B7-H1 on intrahepatic cholangiocarcinoma cells with PD-1 on tumor-infiltrating T cells as a mechanism of immune evasion

J Surg Oncol. 2009 Nov 1;100(6):500-4. doi: 10.1002/jso.21376.

Abstract

Background and objectives: The B7-H1/PD-1 pathway has recently been found to contribute to immune evasion of cancer cells from host immune system. This study aimed to investigate the expression of B7-H1 and its receptor PD-1 and to explore their significance in the progression of intraheptic cholangiocarcinoma (ICC).

Methods: Thirty-one surgically resected ICC tissues and the corresponding cancer adjacent tissues were enrolled from 2006 to 2007. Immunohistochemical studies were performed with antibody of B7-H1, PD-1, CD8, and CD4. Apoptosis status of tumor-infiltrating lymphocytes (TILs) was detected by TUNEL assay.

Results: Expression of B7-H1 and PD-1 was found to be up-regulated in ICC tissues compared with the cancer adjacent tissues. Tumor-related B7-H1 expression was significantly correlated with both tumor differentiation and pTNM stage and was inversely correlated with CD8+ TILs but not CD4+ TILs. TILs in primary carcinoma showed a high level of apoptosis.

Conclusion: B7-H1/PD-1 pathway may be linked to malignant potential of ICC and contribute to tumor immune evasion by promoting CD8+ TILs apoptosis. Thus, this pathway may indeed be a potential therapeutic target in the treatment of this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism*
  • Apoptosis
  • Apoptosis Regulatory Proteins / metabolism*
  • B7-H1 Antigen
  • Bile Duct Neoplasms / immunology*
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cholangiocarcinoma / immunology*
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor
  • Tumor Escape*
  • Up-Regulation

Substances

  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor