Correlation between expression of cyclooxygenase-2 and the presence of CD4+ infiltrating T-lymphocyte in human primary hepatocellular carcinoma

Ya Wei Gao, Yu Xiao Chen, Zhi Ming Wang, Le Du Zhou, Xin Ying Li, Li Xin Li, Qi Zhi Luo, Wei Tian, Chun Yan Fu, Jian Hua Zhou

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background/Aims: Recent studies have found that Cyclooxygenase-2(Cox-2) is frequently inappropriately expressed in primary hepatocellular carcinoma (HCC), suggesting that abnormal Cox-2 expression plays an important role in hepatocarcinogenesis. But it remains controversial in these reports. Moreover, there are only a few studies on the correlation between Cox-2 and infiltrating immunocytes in the tumor-microenvironment. CD4+ tumor-infiltrating lymphocytes (TIL) and infiltrating immunocytes around the tumor are closely correlated to the development of the tumor, but so far no reports are available showing the relationship among Cox-2, CD4+ TIL of tumor and CD4 + infiltrating T-lymphocytes of adjoining non-tumorous (ANT) tissues in tumor-microenvironment. This study is designed to appropriately select and collect patients' specimens to better reflect Cox-2 expression in human HCC, and also to stress the correlation among Cox-2, CD4+ TIL and CD4 + infiltrating T-lymphocytes in the tumor-microenvironment. Methodology: Tumor tissue, and its matched ANT tissue removed less than 1cm from the solid tumor border, were obtained from 25 HCC patients all of whom came from Hunan province, China, and were infected with hepatitis B virus (HBV). Normal liver tissues of 10 hemangiomas were collected as controls. Both Cox-2 expression and the number of CD4+ TIL and CD4+ infiltrating T-lymphocyte were detected by immunohistochemistry, and data were analyzed closely with patients' clinical figures so as to investigate the correlation between the 3 elements. Results: In 25 HCC patients, remarkably higher Cox-2 expression in both tumor and ANT tissues was observed compared with normal liver tissues (p<0.001). The percentage of Cox-2 positive cells was, remarkably, higher in ANT tissues than in tumors (p<0.001). Similarly the distribution of CD4+ T cells was significantly higher in ANT tissue than in tumor tissue (p<0.0001), and also significantly higher in tumor tissue than in normal tissue (p<0.0001). Importantly, in the group of patients with Cox-2-expressing tumors, the number of CD4+ infiltrating T-lymphocyte in ANT tissues was 79.4+9.92/hpf, which is obviously lower (p=0.019) than that of the group with non-Cox-2-expressing tumors with the number of CD4+ infiltrating T-lymphocyte in ANT tissues at 118.13+12.47/hpf. Cox-2 expression of tumors showed a significant negative correlation with number of CD4+ infiltrating T cells of ANT tissues (r=0.499, p=0.024). The number of CD4+ TILs are lower in Cox-2-expressing tumors than in non-Cox-2-expressing tumors, but there was not statistical significance (p=0.057). Conclusions: Taken together we suggest in the tumor-microenvironment of HCC the expression of Cox-2 may inhibit the number CD4+ infiltrating T-lymphocyte in ANT tissues. As a result, Cox-2 overexpression may contribute to both suppression of local immune responses and enhancement of metastatic potential in human HCC.

Original languageEnglish
Pages (from-to)345-350
Number of pages6
Issue number82-83
StatePublished - Mar 2008
Externally publishedYes


  • Adjoining non-tumorous tissues
  • Cox-2, CD4
  • Hepatocellular carcinoma
  • Infiltrating T-lymphocyte


Dive into the research topics of 'Correlation between expression of cyclooxygenase-2 and the presence of CD4+ infiltrating T-lymphocyte in human primary hepatocellular carcinoma'. Together they form a unique fingerprint.

Cite this