Intratumoral regulatory T cells alone or in combination with cytotoxic T cells predict prognosis of hepatocellular carcinoma after resection
Intratumoral regulatory T cells alone or in combination with cytotoxic T cells predict prognosis of hepatocellular carcinoma after resection
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DOI：
10.1007/s12032-011-0006-x
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发表时间：
2012-09-01
期刊：
影响因子：
3.4
通讯作者：
Zheng, Shu-sen
中科院分区：
文献类型：
--
作者：
Chen, Kang-jie;Zhou, Lin;Zheng, Shu-sen
肿瘤浸润淋巴细胞（TIL）代表宿主对癌症的免疫应答。CD 8（+）细胞毒性T细胞（CTL）在消除肿瘤中具有核心作用，而调节性T细胞（TCLs）可以抑制免疫反应。本研究的目的是探讨TIL，特别是TCLs和CTL，在肝细胞癌（HCC）患者切除术后的预后价值。通过免疫组织化学方法对141例随机选择的HCC患者的肿瘤组织中的CD 3（+）、CD 4（+）、CD 8（+）和FoxP 3（+）TIL进行评估。采用Kaplan-Meier和考克斯回归分析，以中位值为界值，评价低密度和高密度TIL亚群对预后的影响。肿瘤内TCLs（P = 0.040）和肿瘤周围CTLs（P = 0.004）的密度是总生存期（OS）的独立因素，但不是无病生存期（DFS）的独立因素。CD 3（+）和CD 4（+）TIL的密度以及T淋巴细胞和CTL的患病率与OS和DFS无关。肿瘤内低T细胞增殖和肿瘤内高CTL的存在是OS的负性独立预后因素（P = 0.001），而肿瘤内低T细胞增殖和肿瘤周围低CTL的存在与DFS改善独立相关（P = 0.008）。此外，联合分析的TCLs和CTL表现出更好的预后性能比任何单独的。此外，较高密度的肿瘤内THBE与肝硬化（P = 0.025）和肿瘤大小增加（P = 0.050）相关。肿瘤环境中的T淋巴细胞是HCC患者有希望的预后参数，其与CTL的组合可以更有效地预测预后。
Tumor-infiltrating lymphocytes (TILs) represent the host immune response to cancer. CD8(+) cytotoxic T cells (CTLs) have a central role in the elimination of tumors, while regulatory T cells (Tregs) can suppress the immune reaction. The aim of this study was to investigate the prognostic value of TILs, especially Tregs and CTLs, in hepatocellular carcinoma (HCC) patients after resection. CD3(+), CD4(+), CD8(+), and FoxP3(+) TILs were assessed by immunohistochemistry in tumor tissue from 141 randomly selected HCC patients. Prognostic effects of low-or high-density TIL subsets were evaluated by Kaplan-Meier and Cox regression analysis using the median values as cutoff. The density of intratumoral Tregs (P = 0.040) and peritumoral CTLs (P = 0.004) were an independent factor for overall survival (OS), but not for disease-free survival (DFS). The density of CD3(+) and CD4(+) TILs, and the prevalence of Tregs and CTLs were associated with neither OS nor DFS. The presence of low intratumoral Tregs with high intratumoral CTLs was a negative independent prognostic factor for OS (P = 0.001), while that of low intratumoral Tregs and low peritumoral CTLs independently correlated with improved DFS (P = 0.008). Moreover, the combined analysis of Tregs and CTLs displayed better prognostic performances than any of them alone. Additionally, higher density of intratumoral Tregs correlated with both the presence of liver cirrhosis (P = 0.025) and increased tumor size (P = 0.050). Tregs within tumor environment are promising prognostic parameters for HCC patients, and their combination with CTLs can predict prognosis more effectively.