B and CTL responses to the ALK protein in patients with ALK-positive ALCL
B and CTL responses to the ALK protein in patients with ALK-positive ALCL
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DOI：
10.1002/ijc.21410
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发表时间：
2006-03-01
影响因子：
6.4
通讯作者：
Pulford, K
中科院分区：
文献类型：
--
作者：
Ait-Taharl, K;Cerundolo, V;Pulford, K
与 ALK 阴性的 ALCL 相比，间变性淋巴瘤激酶 (ALK) 阳性的间变性大细胞淋巴瘤 (ALCL) 的预后良好，这可能是由于 ALK 蛋白的免疫识别所致。我们研究的目的是调查 ALK 阳性 ALCL 中是否存在对 ALK 的 B 细胞和细胞毒性 T 细胞 (CTL) 反应。我们证实，在接受调查的所有 9 名 ALK 阳性 ALCL 患者中均存在针对 ALK 的抗体反应。使用 ELISpot 测定法检测单核血细胞与 2 种 ALK 衍生的 HLA-A*0201 限制性肽：ALKa 和 ALKb 短期培养后的 γ-干扰素 (IFN) T 细胞反应。在所有 7 名 HLA-A*0201 阳性 ALK 阳性 ALCL 患者中均发现显着的 γ-IFN 应答，但在 ALK 阴性 ALCL 患者 (n = 2) 或正常受试者 (n = 6) 中则没有。从 2 名 ALK 阳性 ALCL 患者中培养的 CTL 系（> 95% CD8 阳性）以 MHC-I 类限制方式裂解 ALK 阳性 ALCL 衍生细胞系。这是 ALK 阳性 ALCL 患者中 B 细胞和 CTL 对 ALK 均产生反应的首次报告。这种反应在长期缓解期间持续存在。还描述了使用修饰的痘苗病毒安卡拉 (MVA) 来表达 ALK。我们的研究结果具有潜在的预后价值，并为那些对常规治疗无反应的 ALK 阳性患者提供了治疗选择。 (c) 2005 年 Wiley-Liss, Inc.
Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) has a good prognosis compared to ALK-negative ALCL, possibly as a result of the immune recognition of the ALK proteins. The aim of our study was to investigate the presence of both a B and cytotoxic T cell (CTL) response to ALK in ALK-positive ALCL. We confirmed the presence of an antibody response to ALK in all 9 ALK-positive ALCL patients investigated. An ELISpot assay was used to detect a gamma-interferon (IFN) T cell response after short term culture of mononuclear blood cells with 2 ALK-derived HLA-A*0201 restricted peptides: ALKa and ALKb. A significant gamma-IFN response was identified in all 7 HLA-A*0201-positive ALK-positive ALCL patients but not in ALK-negative ALCL patients (n = 2) or normal subjects (n = 6). CTL lines (> 95% CD8-positive) raised from 2 ALK-positive ALCL patients lysed ALK-positive ALCL derived cell lines in a MHC-Class I restricted manner. This is the first report of both a B cell and CTL response to ALK in patients with ALK-positive ALCL. This response persisted during long-term remission. The use of modified vaccinia virus Ankara (MVA) to express ALK is also described. Our findings are of potential prognostic value and open up therapeutic options for those ALK-positive patients who do not respond to conventional treatment. (c) 2005 Wiley-Liss, Inc.