Spontaneous tumor-specific humoral and cellular immune responses to NY-ESO-1 in hepatocellular carcinoma
Spontaneous tumor-specific humoral and cellular immune responses to NY-ESO-1 in hepatocellular carcinoma
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DOI：
10.1158/1078-0432.ccr-04-0181
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发表时间：
2004-07-01
影响因子：
11.5
通讯作者：
Greten, TF
中科院分区：
文献类型：
--
作者：
Korangy, F;Ormandy, LA;Greten, TF
目的：肝细胞癌（HCC）是世界上第五大常见癌症。虽然有几种治疗HCC的方法，但由于治疗方法效率低下，HCC患者的存活率仍然很低。对于HCC以及其他肿瘤，抗原特异性免疫治疗仍然是一种可行的方法，它依赖于肿瘤相关抗原的定义。NY-ESO-1是癌睾丸抗原家族的一员，是HCC中肿瘤特异性抗原的一种可能候选物。本研究的目的是显示NY-ESO-1在肝细胞癌中的相关性。实验设计：对189例HCC患者的血清样本进行ny - eso -1特异性抗体分析。筛选49例HCC患者HCC组织中NY-ESO-1 mRNA表达情况。选定的患者被随访长达3年，以将他们的免疫反应与他们的临床病程联系起来。分析NY-ESO-1血清阳性患者的NY-ESO-1特异性CD4+和CD8+ t细胞应答，并生成NY-ESO-1+特异性细胞毒t细胞系。结果：49例肿瘤样本中有12例表达NY-ESO-1 mRNA， 189例患者中有23例出现NY-ESO-1特异性抗体反应。这些体液免疫反应伴随着ny - eso -1特异性功能性CD4+和CD8+ t细胞反应。最后，NY-ESO-1的体液反应依赖于表达NY-ESO-1的肿瘤的存在。结论：这是HCC患者对已知肿瘤特异性抗原NY-ESO-1蛋白自发免疫反应的首次报道。我们的数据支持免疫治疗策略治疗HCC的可能性。
Purpose: Hepatocellular carcinoma (HCC) is the fifth most common cancer around the world. Although several therapeutic approaches for treatment of HCC are available, survival rates for HCC patients are still very poor because of inefficient treatment options. For HCC, as well as other tumors, antigen-specific immunotherapy remains a viable approach that is dependent on the definition of tumor-associated antigens. NY-ESO-1, a member of the cancer testis antigen family, is one possible candidate for a tumor-specific antigen in HCC. The aim of this study was to show the relevance of NY-ESO-1 in hepatocellular carcinoma.Experimental Design: Sera samples from 189 HCC patients were analyzed for NY-ESO-1-specific antibodies. Forty-nine HCC patients were screened for NY-ESO-1 mRNA expression in HCC tissue. Selected patients were followed for up to 3 years to correlate their immune response with their clinical course of events. NY-ESO-1-specific CD4+ and CD8+ T-cell responses from NY-ESO-1 seropositive patients were analyzed and a NY-ESO-1+ specific cytotoxic T-cell line was generated.Results: Twelve of 49 analyzed tumor samples expressed NY-ESO-1 mRNA and 23 of 189 patients showed NY-ESO-1-specific antibody responses. These humoral immune responses were accompanied by NY-ESO-1-specific functional CD4+ and CD8+ T-cell responses. Finally, NY-ESO-1 humoral responses were dependent on the presence of NY-ESO-1-expressing tumors.Conclusions: This is the first report of a spontaneous immune response in HCC patients to a known tumor-specific antigen, NY-ESO-1 protein. Our data favor the possibility of immunotherapeutic strategies for the treatment of HCC.