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.
Ohno
Yumiko
Y
Department of Obstetrics and Gynecology, Kanazawa University, Graduate School of Medical Science, Ishikawa, Japan.
Ohno
Satoshi
S
Suzuki
Nobutaka
N
Kamei
Tsutomu
T
Inagawa
Hiroyuki
H
Soma
Gen-Ichiro
G
Inoue
Masaki
M
D000328:Adult; D000368:Aged; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology; D002277:Carcinoma / Q000201:enzymology*; D051546:Cyclooxygenase 2; D016889:Endometrial Neoplasms / Q000201:enzymology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008565:Membrane Proteins; D008875:Middle Aged; D009215:Myometrium / Q000378:metabolism; D009389:Neovascularization, Pathologic; D011379:Prognosis; D016016:Proportional Hazards Models; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012008:Recurrence; D013997:Time Factors
D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases