Role of cyclooxygenase-2 in immunomodulation and prognosis of endometrial carcinoma
Role of cyclooxygenase-2 in immunomodulation and prognosis of endometrial carcinoma
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DOI：
10.1002/ijc.20777
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发表时间：
2005-05-01
影响因子：
6.4
通讯作者：
Inoue, M
中科院分区：
文献类型：
--
作者：
Ohno, Y;Ohno, S;Inoue, M
虽然有几种假说解释了恶性肿瘤免疫特权状态的机制，但确切的途径仍有待探索。环氧合酶(COX)-2在肿瘤血管生成和细胞凋亡抑制中起重要作用，但其在免疫调节中的作用尚未见报道。我们评价了环氧合酶-2在子宫内膜癌中的表达及其对免疫活性细胞向肿瘤细胞巢的渗透的影响。对70例子宫内膜癌根治性切除患者的组织标本进行COX-2表达和宿主免疫状态(CD8+T细胞)检测。COX-2的表达与FIGO分期和肌层侵袭有关，但无统计学意义。癌细胞巢内CD8(+)T细胞(Nest CD8)与COX-2表达水平呈负相关(p=0.0006)。Cox‘s多因素分析显示，Nest CD8是患者生存的独立预测因子(危险比=10.300，P=0.0304)。在单因素分析中，COX-2的表达水平是疾病复发的显著预测因素(p=0.0294)，但在多因素分析中，COX-2的表达水平不是疾病复发的显著预测因素(p=0.5949)。总之，在子宫内膜癌患者中，增加Nest CD8产生了生存优势。此外，肿瘤产生的COX-2减少了CD8(+)T细胞对癌细胞巢的渗透，可能使肿瘤避开免疫监视。(C)2004年Wiley-Liss公司
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.