Restoration of Endogenous Retrovirus Infectivity Impacts Mouse Cancer Models

Cancer Immunol Res. 2018 Nov;6(11):1292-1300. doi: 10.1158/2326-6066.CIR-18-0038. Epub 2018 Aug 24.

Abstract

Mouse models have been instrumental in establishing fundamental principles of cancer initiation and progression and continue to be invaluable in the discovery and further development of cancer therapies. Nevertheless, important aspects of human disease are imperfectly approximated in mouse models, notably the involvement of endogenous retroviruses (ERVs). Replication-defective ERVs, present in both humans and mice, may affect tumor development and antitumor immunity through mechanisms not involving infection. Here, we revealed an adverse effect of murine ERVs with restored infectivity on the behavior of mouse cancer models. In contrast to human cancer, where infectious ERVs have never been detected, we found that ERV infectivity was frequently restored in transplantable, as well as genetic, mouse cancer models. Such replication-competent, ERV-derived retroviruses were responsible for unusually high expression of retroviral nucleic acids and proteins in mouse cancers. Infectious ERV-derived retroviruses produced by mouse cancer cells could directly infect tumor-infiltrating host immune cells and fundamentally modified the host's immune defenses to cancer, as well as the outcome of immunotherapy. Therefore, infectious retroviruses, variably arising in mouse cancer models, but not in human cancer, have the potential to confound many immunologic studies and should be considered as a variable, if not altogether avoided. Cancer Immunol Res; 6(11); 1292-300. ©2018 AACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Endogenous Retroviruses / pathogenicity*
  • Female
  • Leukemia Virus, Murine / genetics
  • Leukemia Virus, Murine / pathogenicity
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / virology*
  • Positive Regulatory Domain I-Binding Factor 1 / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Retroviridae Infections / virology
  • Viral Tropism / physiology

Substances

  • Prdm1 protein, mouse
  • Positive Regulatory Domain I-Binding Factor 1
  • Braf protein, mouse
  • Proto-Oncogene Proteins B-raf