Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection
Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection
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DOI：
10.1200/jco.2006.09.4565
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发表时间：
2007-06-20
影响因子：
45.3
通讯作者：
Tang, Zhao-You
中科院分区：
文献类型：
--
作者：
Gao, Qiang;Qiu, Shuang-Jian;Tang, Zhao-You
目的探讨肿瘤浸润性淋巴细胞（TILs），尤其是调节性T细胞（TCLs）在肝细胞癌（HCC）患者术后的预后价值。方法应用免疫组织化学方法检测302例HCC患者的组织芯片中CD3（+）、CD4（+）、CD8（+）、Foxp3阳性和颗粒酶B阳性TILs。结果CD3（+）、CD4（+）、CD8（+）TIL与总生存期（OS）和无病生存期（DFS）均无相关性。肿瘤内低TcB的存在与肿瘤内高活化的CD8（+）细胞毒性细胞（CTL）的存在相结合，是改善DFS（P = 0.001）和OS（P <0.0001）的独立预后因素。肿瘤内高T淋巴细胞数和低活化CTL组的5年OS和DFS率分别为24.1%和19.8%，而肿瘤内低T淋巴细胞数和高活化CTL组的5年OS和DFS率分别为64.0%和59.4%。单独瘤内TdR（P = 0.001）或瘤内激活的CTL（P = 0.001）单独也是OS的独立预测因子。此外，高TGFAP密度与肿瘤无包膜和无肿瘤包膜相关。（P= 0.032）和肿瘤血管浸润的存在结论T细胞亚群与HCC侵袭性有关，调节性T细胞和细胞毒性T细胞的平衡是HCC复发和生存的一个有前景的独立预测因子。TcB的耗竭和效应T细胞的伴随刺激的组合可能是减少复发和延长手术后存活的有效免疫疗法。
PurposeTo investigate the prognostic value of tumor-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in hepatocellular carcinoma (HCC) patients after resection.Patients and MethodsCD3(+), CD4(+), CD8(+), Foxp3-positive, and granzyme B-positive TILs were assessed by immunohistochemistry in tissue microarrays containing HCC from 302 patients. Prognostic effects of low- or high-density TIL subsets were evaluated by Cox regression and Kaplan-Meier analysis using median values as cutoff.ResultsCD3(+), CD4(+), CD8(+) TILs were associated with neither overall survival (OS) nor disease-free survival (DFS). The presence of low intratumoral Tregs in combination with high intratumoral activated CD8(+) cytotoxic cells (CTLs), a balance toward CTLs, was an independent prognostic factor for both improved DFS (P = .001) and OS (P < .0001). Five-year OS and DFS rates were only 24.1% and 19.8% for the group with intratumoral high Tregs and low activated CTLs, compared with 64.0% and 59.4% for the group with intratumoral low Tregs and high activated CTLs, respectively. Either intratumoral Tregs alone (P = .001) or intratumoral activated CTLs (P = .001) alone is also an independent predictor for OS. In addition, high Tregs density was associated with both absence of tumor encapsulation (P= .032) and presence of tumor vascular invasion (P = .031).ConclusionTregs are associated with HCC invasiveness, and intratumoral balance of regulatory and cytotoxic T cells is a promising independent predictor for recurrence and survival in HCC. A combination of depletion of Tregs and concomitant stimulation of effector T cells may be an effective immunotherapy to reduce recurrence and prolong survival after surgery.