Increased expression of cyclooxygenase-2 and increased infiltration of regulatory T cells in tumors of patients with hepatocellular carcinoma

Digestion. 2009;79(3):169-76. doi: 10.1159/000210266. Epub 2009 Mar 30.

Abstract

Background: Studies on Cox-2 and Foxp3+ regulatory T cells (Treg) in hepatocellular carcinoma (HCC) showed that Treg suppress local immune response in a Cox-2-dependent fashion.

Aims: To investigate Cox-2 expression, Foxp3+ Treg infiltration and CD4+ T cell frequency in HCC tumors.

Methods: Tumors and the corresponding nontumor hepatitis B virus-related liver tissues from 40 HCC patients with hepatitis B virus infection, plus 10 liver samples from patients with hemangioma as controls, were assessed for Cox-2 expression, Foxp3+ Treg and total CD4+ T cell numbers using immunohistochemistry. Serum TGF-beta1 was assessed by ELISA.

Results: Reduced Cox-2 expression, increased Treg and increased CD4+ T cells were shown in tumor as compared with nontumor tissues. Moreover, of 40 tumor tissues, 23 that expressed Cox-2 showed increased Foxp3+ Treg and reduced CD4+ T cells compared with the remaining 17 that did not express Cox-2. Correlation analyses showed that within tumors Treg infiltration correlated positively with Cox-2 expression, and that Treg infiltration or Cox-2 expression correlated negatively with CD4+ T cells. Additionally, serum TGF-beta1 was higher in HCC patients than in controls.

Conclusion: Within tumors, Cox-2 expression, Treg infiltration and CD4+ T cell frequency were increased, and the Cox-2 expression correlated positively with Treg infiltration and negatively with CD4+ T cell frequency.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / genetics*
  • Cyclooxygenase 2 / biosynthesis*
  • Female
  • Forkhead Transcription Factors
  • Gene Expression
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / genetics*
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / metabolism
  • Transforming Growth Factor beta1

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Transforming Growth Factor beta1
  • Cyclooxygenase 2