Cherkasova Elena, Scrivani Claire, Doh Susan, Weisman Quinn, Takahashi Yoshiyuki, Harashima Nanae, Yokoyama Hisayuki, Srinivasan Ramaprasad, Linehan W Marston, Lerman Michael I, Childs Richard W
Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland.
Urologic Oncology Branch, NCI, NIH, Bethesda, Maryland.
Cancer Res. 2016 Apr 15;76(8):2177-85. doi: 10.1158/0008-5472.CAN-15-3139. Epub 2016 Feb 9.
VHL-deficient clear cell renal cell carcinomas (ccRCC), the most common form of kidney cancer, express transcripts derived from the novel human endogenous retrovirus HERV-E (named CT-RCC HERV-E). In this study, we define a transcript encoding the entire envelope gene of HERV-E as expressed selectively in ccRCC tumors, as distinct from normal kidney tissues or other tumor types. Sequence analysis of this envelope transcript revealed long open reading frames encoding putative surface and transmembrane envelope proteins. Retroviral envelopes are known to be capable of eliciting immunity in humans. Accordingly, we found that HLA-A0201-restricted peptides predicted to be products of the CT-RCC HERV-E envelope transcript-stimulated CD8(+) T cells, which could recognize HLA-A0201-positive HERV-E-expressing kidney tumor cells. Overall, our results offer evidence of unique HERV-E envelope peptides presented on the surface of ccRCC cells, offering potentially useful tumor-restricted targets for T-cell-based immunotherapy of kidney cancer. Cancer Res; 76(8); 2177-85. ©2016 AACR.
VHL基因缺陷型肾透明细胞癌（ccRCC）是最常见的肾癌形式，它表达源自新型人类内源性逆转录病毒HERV-E（命名为CT-RCC HERV-E）的转录本。在本研究中，我们定义了一种编码HERV-E完整包膜基因的转录本，该转录本在ccRCC肿瘤中选择性表达，与正常肾组织或其他肿瘤类型不同。对该包膜转录本的序列分析揭示了编码假定的表面和跨膜包膜蛋白的长开放阅读框。已知逆转录病毒包膜能够在人类中引发免疫反应。因此，我们发现预测为CT-RCC HERV-E包膜转录本产物的HLA-A0201限制性肽可刺激CD8(+) T细胞，这些T细胞能够识别表达HLA-A0201的HERV-E阳性肾肿瘤细胞。总体而言，我们的结果提供了ccRCC细胞表面呈现独特的HERV-E包膜肽的证据，为基于T细胞的肾癌免疫治疗提供了潜在有用的肿瘤限制性靶点。《癌症研究》；76(8)；2177 - 85。©2016美国癌症研究协会。
