Strong CD8+ T-cell responses against tumor-associated antigens prolong the recurrence-free interval after tumor treatment in patients with hepatocellular carcinoma
Strong CD8+ T-cell responses against tumor-associated antigens prolong the recurrence-free interval after tumor treatment in patients with hepatocellular carcinoma
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DOI：
10.1007/s00535-009-0155-2
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发表时间：
2010-04-01
影响因子：
6.3
通讯作者：
Imawari, Michio
中科院分区：
文献类型：
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作者：
Hiroishi, Kazumasa;Eguchi, Junichi;Imawari, Michio
我们研究了肿瘤特异性CD 8（+）T细胞应答是否影响无瘤生存率，以及CD 8（+）T细胞对肿瘤相关抗原（TAAs）的应答与肝细胞癌（HCC）患者肿瘤治疗后临床病程的关系。治疗后1个月超声检查、CT和/或MRI检查均未检出HCC的患者纳入研究。肝癌治疗前后TAA分析（磷脂酰肌醇蛋白聚糖-3，NY-ESO-1，和法师-1）特异性CD 8（+）T细胞应答用干扰素-γ酶联免疫斑点（ELISpot）测定进行评价，使用外周CD 8（+）T细胞，单核细胞，104种20-mer合成肽，10个残基重叠，跨越整个3个TAA，20例中有16例（80%）在治疗前或治疗后显示阳性应答（1份/千日元10个TAA特异性细胞/10（5）个CD 8（+）T细胞）。当我们对20例患者的无肿瘤期的预后因素进行单变量分析时，血小板计数、凝血酶原时间和治疗后TAA特异性CD 8（+）T细胞数量是显著因素（分别为P = 0.027、0.030和0.004）。在多变量分析中，TAA特异性CD 8（+）T细胞应答的大小（每千日元40个TAA特异性细胞/10（5）个CD 8（+）T细胞）是延长无瘤期的唯一显著预后因素（风险比0.342，P = 0.022）。肝癌患者局部治疗后，应考虑通过使用肽疫苗等手段诱导TAA特异性细胞毒性T淋巴细胞的免疫治疗，用于临床应用。
We investigated whether tumor-specific CD8(+) T-cell responses affect tumor-free survival as well as the relationship between CD8(+) T-cell responses against tumor-associated antigens (TAAs) and the clinical course after tumor treatment in patients with hepatocellular carcinoma (HCC).Twenty patients with HCC that were treated by radiofrequency ablation or trans-catheter chemo-embolization (TACE) and in whom HCC was undetectable by ultrasonography, CT, and/or MRI 1 month after treatment were enrolled in the study. Before and after treatment for HCC, analyses of TAA (glypican-3, NY-ESO-1, and MAGE-1)-specific CD8(+) T-cell responses were evaluated with an interferon-gamma enzyme-linked immunospot (ELISpot) assay using peripheral CD8(+) T-cells, monocytes, and 104 types of 20-mer synthetic peptide overlapping by 10 residues and spanning the entirety of the 3 TAAs.Sixteen out of 20 patients (80%) showed a positive response (a parts per thousand yen10 TAA-specific cells/10(5) CD8(+) T-cells) before or after treatment. When we performed univariate analysis of prognostic factors for the tumor-free period in the 20 patients, platelet count, prothrombin time, and the number of TAA-specific CD8(+) T-cells after treatment were significant factors (P = 0.027, 0.030, and 0.004, respectively). In multivariate analysis, the magnitude of the TAA-specific CD8(+) T-cell response (a parts per thousand yen40 TAA-specific cells/10(5) CD8(+) T-cells) was the only significant prognostic factor for a prolonged tumor-free interval (hazard ratio 0.342, P = 0.022).Our results suggest that strong TAA-specific CD8(+) T-cell responses suppress the recurrence of HCC. Immunotherapy to induce TAA-specific cytotoxic T lymphocytes by means such as the use of peptide vaccines should be considered for clinical application in patients with HCC after local therapy.