Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Asahikawa, Japan.
Br J Haematol. 2013 Feb;160(3):331-42. doi: 10.1111/bjh.12136. Epub 2012 Dec 4.
Nasal natural killer (NK)/T cell lymphoma (NNKTL) is associated with Epstein-Barr virus (EBV). The present study analysed gene expression patterns of the NNKTL cell lines SNK6, SNK1 and SNT8, which are positive for EBV and latent membrane protein (LMP)-1, using a complementary DNA array analysis. We found that CD70 was specifically expressed in SNK6 and SNT8. Reverse transcription polymerase chain reaction and flow cytometric analyses confirmed that CD70 was expressed in all 3 NNKTL cell lines, but not in the other EBV-positive NK-cell lines. In vitro studies showed that NNKTL cell lines proliferated, in a dose-dependent fashion, in response to exogenous soluble CD27, which is the ligand for CD70. In NNKTL patients, we confirmed that the CD70 was expressed on the lymphoma cells in NNKTL tissues and that soluble CD27 was present in sera at higher levels as compared to healthy individuals. Finally, complement-dependent cytotoxicity assay showed that anti-CD70 antibody mediated effective complement-dependent killing of NNKTL cells and the affected target CD70 expression on the cells. These results suggest that CD70 acts as a functional receptor binding to soluble CD27, resulting in lymphoma progression and that immunotherapy using anti-CD70 antibody may be a potential candidate for treatment for NNKTL.
鼻腔自然杀伤 (NK)/T 细胞淋巴瘤 (NNKTL) 与 Epstein-Barr 病毒 (EBV) 有关。本研究采用 cDNA 芯片分析方法分析了 EBV 和潜伏膜蛋白 (LMP)-1 阳性的 NNKTL 细胞系 SNK6、SNK1 和 SNT8 的基因表达模式。我们发现 CD70 特异性表达于 SNK6 和 SNT8。逆转录聚合酶链反应和流式细胞术分析证实 CD70 在所有 3 种 NNKTL 细胞系中表达，但在其他 EBV 阳性 NK 细胞系中不表达。体外研究表明，NNKTL 细胞系以剂量依赖性方式增殖，对细胞表面表达的可溶性 CD27（CD70 的配体）产生反应。在 NNKTL 患者中，我们证实 CD70 在 NNKTL 组织中的淋巴瘤细胞上表达，并且与健康个体相比，血清中存在更高水平的可溶性 CD27。最后，补体依赖性细胞毒性测定表明，抗 CD70 抗体介导了对 NNKTL 细胞的有效补体依赖性杀伤，并且影响了细胞上的靶标 CD70 表达。这些结果表明，CD70 作为一种功能性受体与可溶性 CD27 结合，导致淋巴瘤进展，并且使用抗 CD70 抗体的免疫疗法可能是治疗 NNKTL 的潜在候选方法。
