Role of cyclooxygenase-2 in immunomodulation and prognosis of endometrial carcinoma

Although there are several hypotheses explaining the mechanisms of immune-privileged status of malignant tumor, the exact pathway has yet to be explored. Cyclooxygenase (COX)-2 plays a vital role in prognosis of cancer patients in terms of contribution to neoangiogenesis and apoptosis inhibition; however, the impact of COX-2 in immunomodulation has not been reported. We have evaluated the expression of COX-2 and its impact on infiltration of immune-competent cells into the tumor cell nest in endometrial carcinoma. Tissue specimens from 70 endometrial carcinoma patients who had undergone a curative resection were evaluated for COX-2 expression and host immune status (CD8(+) T cells). COX-2 expression was associated with FIGO stage and myometrial invasion, but there was no statistically significant impact. CD8(+) T cells within cancer cell nest (Nest CD8) were inversely correlated with the expression level of COX-2 (p = 0.0006). Nest CD8 became an independent predictor of patient survival (Hazard ratio = 10.300, P = 0.0304) in Cox's multivariate analysis. The expression level of COX-2 was found to be a significant predictor of disease relapse in univariate analysis (p = 0.0294) but not in multivariate analysis (p = 0.5949). In conclusion, increased nest CD8 produced a Survival advantage in endometrial carcinoma patients. Moreover, tumor-produced COX-2, which reduces the infiltration of CD8(+) T cells into cancer cell nests, may allow tumors to avoid immune surveillance. (C) 2004 Wiley-Liss, Inc.