Tumor Cyclooxygenase-2 Gene Suppresses Local Immune Responses in Patients with Hepatocellular Carcinoma

Abstract

In several neoplastic diseases including hepatocellular carcinoma (HCC) immunosuppression is correlated with disease stage, progression and outcome. Moreover, recent studies have demonstrated that cyclooxygenase-2 (COX-2) enhances tumor growth in HCCs. The present study analyzed the correlation between local immune responses and COX-2 gene expression levels in patients with primary HCCs. Fresh tissues were obtained from 59 patients who underwent resection of an HCC. The COX-2 gene expression levels were quantified by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and compared with the CD8+ T cell densities detected by immunohistochemistry. COX-2 gene expression was detected in 35 of the 59 tumors. The CD8+ T cell density in COX-2-expressing tumors (6.1 cells/high-power field (HPF), x200 magnification) was suppressed compared with that in non-COX-2-expressing tumors (13.6 cells/HPF, P = 0.009). Tumor COX-2 gene expression was associated with a poorer disease-free survival rate. Elevation of the tumor COX-2 level is correlated with the suppression of local immune responses in HCCs, suggesting that COX-2 plays a role in early tumor recurrence in the residual liver in patients after HCC resection.