Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells
Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells
复制标题
DOI：
10.1172/jci34409
复制
发表时间：
2008-03-01
影响因子：
15.9
通讯作者：
Childs, Richard W.
中科院分区：
文献类型：
--
作者：
Takahashi, Yoshiyuki;Harashima, Nanae;Childs, Richard W.
在造血干细胞移植(HSCT)中输注的供者淋巴细胞已被证明可以治愈血液系统恶性肿瘤患者。然而，关于HSCT对转移性实体瘤的影响，我们知之甚少。因此，迫切需要更好地了解介导肿瘤消退的免疫细胞及其靶抗原，以开发更有效的实体肿瘤HSCT方法。在这里，我们报告了非清髓性HSCT后转移性肾细胞癌(RCC)的消退，这与移植物抗肿瘤效应一致。我们在非清髓性HSCT患者的血液中检测到RCC反应性供者来源的CD8(+)T细胞。通过基因表达克隆，我们确定了一个10肽(CT-RCC-1)作为肾癌特异性CD8(+)T细胞的靶抗原。编码该抗原的基因来源于人内源性逆转录病毒(HERV)E型，在肾癌细胞系和新鲜肾癌组织中表达，而在正常肾脏或其他组织中不表达。我们认为这是第一个使用同种异体T细胞从接受HSCT的患者身上鉴定出的实体肿瘤抗原。这些数据表明，HERV-E在肾癌中被激活，并编码一种过表达的免疫原性抗原，因此为细胞免疫提供了一个潜在的靶点。
Transplanted donor lymphocytes infused during hematopoietic stem cell transplantation (HSCT) have been shown to cure patients with hematological malignancies. However, less is known about the effects of HSCT on metastatic solid tumors. Thus, a better understanding of the immune cells and their target antigens that mediate tumor regression is urgently needed to develop more effective HSCT approaches for solid tumors. Here we report regression of metastatic renal cell carcinoma (RCC) in patients following nonmyeloablative HSCT consistent with a graft-versus-tumor effect. We detected RCC-reactive donor-derived CD8(+) T cells in the blood of patients following nonmyeloablative HSCT. Using cDNA expression cloning, we identified a 10-mer peptide (CT-RCC-1) as a target antigen of RCC-specific CD8(+) T cells. The genes encoding this antigen were found to be derived from human endogenous retrovirus (HERV) type E and were expressed in RCC cell lines and fresh RCC tissue but not in normal kidney or other tissues. We believe this to be the first solid tumor antigen identified using allogeneic T cells from a patient undergoing HSCT. These data suggest that HERV-E is activated in RCC and that it encodes an overexpressed immunogenic antigen, therefore providing a potential target for cellular immunity.