HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy

Clear cell renal cell carcinoma (ccRCC), despite having a low mutational burden, is considered immunogenic because it occasionally undergoes spontaneous regressions and often responds to immunotherapies. The signature lesion in ccRCC is inactivation of the VHL tumor suppressor gene and consequent upregulation of the HIF transcription factor. An earlier case report described a ccRCC patient who was cured by an allogeneic stem cell transplant and later found to have donor-derived T cells that recognized a ccRCC-specific peptide encoded by a HIF-responsive endogenous retrovirus (ERV), ERVE-4. We report that ERVE-4 is one of many ERVs that are induced by HIF, translated into HLA-bound peptides in ccRCCs, and…

• UD
  U.S. Department of Defense

  Award: W81XWH-22-1-0096
• HH
  Howard Hughes Medical Institute

  Award: 5R35CA210068
• BC
  Breast Cancer Research Foundation
• G
  GlaxoSmithKline

  Award: GSK3685032
• DM
  Dr. Miriam and Sheldon G. Adelson Medical Research Foundation

  Awards: R01CA279391, R01HL157174, U54CA272688, R01CA285308
• YC
  Yale Cancer Center

  Award: P30CA01635
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

  Award: 225660
• NI
  National Institutes of Health

  Award: R01GM123002
• NC
  National Cancer Institute

  Award: 5R01CA155010