Epitope mapping of spontaneous autoantibodies to anaplastic lymphoma kinase (ALK) in non-small cell lung cancer.
Epitope mapping of spontaneous autoantibodies to anaplastic lymphoma kinase (ALK) in non-small cell lung cancer.
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DOI：
10.18632/oncotarget.21182
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发表时间：
2017-11-03
期刊：
影响因子：
--
通讯作者：
Chiarle R
中科院分区：
文献类型：
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作者：
Awad MM;Mastini C;Blasco RB;Mologni L;Voena C;Mussolin L;Mach SL;Adeni AE;Lydon CA;Sholl LM;Jänne PA;Chiarle R
间变性淋巴瘤激酶 (ALK) 被免疫系统识别为肿瘤抗原，临床前证据表明，使用基于疫苗的方法也可以成功地免疫靶向 ALK 重排的 NSCLC。与 ALK 重排淋巴瘤相比，ALK 重排 NSCLC 患者自发 ALK 免疫反应的频率和临床意义尚不清楚。我们开发了一种酶联免疫吸附测定 (ELISA) 来测量非小细胞肺癌患者的抗 ALK 抗体水平，并绘制 ALK 胞质结构域内的特定肽表位序列。 ELISA 方法显示与标准免疫细胞化学方法测量的 ALK 抗体滴度具有良好的相关性。 53 名 ALK 阳性 NSCLC 患者中的 9 名 (17.0%) 和 38 名 ALK 阴性 NSCLC 患者中的 0 名 (0%) 检测到强抗 ALK 抗体反应 (P<0.01)，并且 ALK 阳性患者的平均抗体水平显着高于 ALK 阴性 NSCLC 患者 (P=0.02)。在个体患者中，自身抗体识别 ALK 胞质结构域中的不同表位，其中大多数聚集在酪氨酸激酶结构域之外。高 ALK 自身抗体水平的存在是否会为该患者群体带来更良好的预后，值得进一步研究。
The anaplastic lymphoma kinase (ALK) is recognized by the immune system as a tumor antigen, and preclinical evidence suggests that ALK-rearranged NSCLCs can also be successfully targeted immunologically using vaccine-based approaches. In contrast to ALK-rearranged lymphomas, the frequency and clinical significance of spontaneous ALK immune responses in patients with ALK-rearranged NSCLCs are largely unknown. We developed an enzyme-linked immunosorbent assay (ELISA) to measure anti-ALK antibody levels and mapped specific peptide epitope sequences within the ALK cytoplasmic domain in patients with non-small cell lung cancer. The ELISA method showed good correlation with ALK antibody titers measured with a standard immunocytochemical approach. Strong anti-ALK antibody responses were detected in 9 of 53 (17.0%) ALK-positive NSCLC patients and in 0 of 38 (0%) ALK-negative NSCLC patients (P<0.01), and the mean antibody levels were significantly higher in ALK-positive than in ALK-negative NSCLC patients (P=0.02). Across individual patients, autoantibodies recognized different epitopes in the ALK cytoplasmic domain, most of which clustered outside the tyrosine kinase domain. Whether the presence of high ALK autoantibody levels confers a more favorable prognosis in this patient population warrants further investigation.