Prognostic impact of tumor infiltrating CD8+T cells in association with cell proliferation in ovarian cancer patients - a study of the OVCAD consortium
Prognostic impact of tumor infiltrating CD8+T cells in association with cell proliferation in ovarian cancer patients - a study of the OVCAD consortium
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DOI：
10.1186/1471-2407-13-422
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发表时间：
2013-09-17
期刊：
影响因子：
3.8
通讯作者：
Castillo-Tong, Dan Cacsire
中科院分区：
文献类型：
--
作者：
Bachmayr-Heyda, Anna;Aust, Stefanie;Castillo-Tong, Dan Cacsire
背景：上皮性卵巢癌是妇科恶性肿瘤中最致命的一种。临床病理因素不允许精确的预后，不能提供指导的具体治疗。在这项研究中，我们评估了肿瘤浸润的CD 8 + T细胞与Ki 67增殖指数，并评估其预后的影响EOC samples.Methods：CD 8+细胞和Ki 67增殖指数进行了免疫组化测定的组织芯片，包括203原发性上皮性卵巢肿瘤。此外，用RT-qPCR评估CD 8基因表达。使用Pearson相关系数、ANOVA或T检验或Fischer精确检验分析相关性。采用Kaplan-Meier法和考克斯回归模型分析CD 8+浸润淋巴细胞密度与肿瘤细胞增殖的关系。肿瘤中无Ki 67+细胞的上皮性卵巢癌患者的死亡风险是肿瘤中有Ki 67+细胞的人群的3倍以上（风险比（HR）= 3.34，95% CI 1.59-7.04）。高CD 8+细胞浸润与总生存率的提高相关（HR = 0.82，95% CI 0.73-0.92）。Ki 67肿瘤的卵巢癌患者的总生存率显着降低，可能是由于对铂类化疗无反应或反应不良。此外，证实了高密度的肿瘤浸润细胞毒性T淋巴细胞与更好的总生存期的相关性。
Background: Epithelial ovarian cancer is one of the most lethal gynecologic malignancies. Clinicopathological factors do not permit precise prognosis and cannot provide guidance to specific treatments. In this study we assessed tumor infiltrating CD8+ T cells in association with Ki67 proliferation index and evaluated their prognostic impact in EOC samples.Methods: CD8+ cells and Ki67 proliferation index were immunohistochemically determined on tissue microarrays including 203 primary epithelial ovarian tumors. Additionally, CD8 gene expression was assessed with RT-qPCR. Correlations were analyzed using Pearson's correlation coefficients, ANOVA or T-test, or Fischer's exact tests. Prognostic impact was evaluated using the Kaplan-Meier method and Cox regression model.Results: The density of CD8+ infiltrating lymphocytes did not correlate with tumor cell proliferation. Epithelial ovarian cancer patients with no Ki67+ cells in the tumor had a more than three times higher risk to die compared to the population with Ki67+ cells in the tumor (Hazard ratio (HR) = 3.34, 95% CI 1.59-7.04). High CD8+ cell infiltration was associated with improved overall survival (HR = 0.82, 95% CI 0.73-0.92).Conclusions: The density of tumor infiltrating lymphocytes is independent of tumor cell proliferation. Ovarian cancer patients with Ki67-tumors showed a significantly reduced overall survival, presumably due to no or poor response to platinum-based chemotherapy. Moreover, the association of high densities of tumor infiltrating cytotoxic T lymphocytes with a better overall survival was confirmed.