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Detection of an Immunogenic HERV-E Envelope with Selective Expression in Clear Cell Kidney Cancer
Elena Cherkasova1, Claire Scrivani1, Susan Doh1
1Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland.
Abstract:
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 Res; 76(8); 2177-85. ©2016 AACR.
Insights
Clear cell renal cell carcinoma (ccRCC), a common kidney cancer, uniquely expresses a human endogenous retrovirus HERV-E envelope transcript. This transcript provides potential targets for T-cell-based immunotherapy against kidney cancer.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer.
- VHL-deficient ccRCC tumors express transcripts from the human endogenous retrovirus HERV-E, termed CT-RCC HERV-E.
Purpose of the Study:
- To define the CT-RCC HERV-E transcript and its encoded proteins.
- To investigate the immunogenicity of CT-RCC HERV-E-derived peptides in ccRCC.
Main Methods:
- Sequence analysis of the CT-RCC HERV-E envelope transcript.
- Identification of HLA-A*0201-restricted peptides.
- CD8(+) T cell stimulation assays.
- Analysis of T cell recognition of tumor cells.
Main Results:
- A specific HERV-E envelope transcript is selectively expressed in ccRCC tumors.
- The transcript encodes putative surface and transmembrane envelope proteins.
- CT-RCC HERV-E-derived peptides stimulate CD8(+) T cells.
- These T cells recognize HERV-E-expressing kidney tumor cells.
Conclusions:
- Unique HERV-E envelope peptides are presented on ccRCC cells.
- These peptides represent potential tumor-restricted targets for kidney cancer immunotherapy.
- The findings support the development of T-cell-based therapies targeting HERV-E in ccRCC.
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