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.

Cancer Research
|February 11, 2016
PubMed

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.