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-A*0201-restricted peptides predicted to be products of the CT-RCC HERV-E envelope transcript stimulated CD8+ T cells which could recognize HLA-A*0201-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 research. 2016 Feb 09 [Epub ahead of print]
Elena Cherkasova, Claire Scrivani, Susan Doh, Quinn Weisman, Yoshiyuki Takahashi, Nanae Harashima, Hisayuki Yokoyama, Ramaprasad Srinivasan, W Marston Linehan, Micheal I Lerman, Richard W Childs
Hematology, National Heart, Lung and Blood Institute. , Hematology, National Heart, Lung and Blood Institute. , Hematology, National Heart, Lung and Blood Institute. , Hematology, National Heart, Lung and Blood Institute. , Hematology, National Heart, Lung and Blood Institute. , Department of Immunotherapeutics, Tokyo Medical and Dental University. , Hematology, National Heart, Lung and Blood Institute. , Urologic Oncology Branch, National Cancer Institute, National Institutes of Health. , Urologic Oncology Branch, National Cancer Institute, National Institutes of Health. , Affina Biotechnologies, Inc. , Hematology, National Heart, Lung, and Blood Institute, National Institutes of Health