Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor

Cancer Cell. 2018 Apr 9;33(4):620-633.e6. doi: 10.1016/j.ccell.2018.03.003.


The canine transmissible venereal tumor (CTVT) is a clonally transmissible cancer that regresses spontaneously or after treatment with vincristine, but we know little about the regression mechanisms. We performed global transcriptional, methylation, and functional pathway analyses on serial biopsies of vincristine-treated CTVTs and found that regression occurs in sequential steps; activation of the innate immune system and host epithelial tissue remodeling followed by immune infiltration of the tumor, arrest in the cell cycle, and repair of tissue damage. We identified CCL5 as a possible driver of CTVT regression. Changes in gene expression are associated with methylation changes at specific intragenic sites. Our results underscore the critical role of host innate immunity in triggering cancer regression.

Keywords: CCL5; cancer; dog; epithelial; innate immunity; melanoma; methylation; regression; transmissible; vincristine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Checkpoints
  • Chemokine CCL5 / genetics
  • DNA Methylation
  • Dog Diseases / drug therapy*
  • Dog Diseases / genetics
  • Dogs
  • Female
  • Gene Expression Profiling / veterinary*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks / drug effects*
  • Immunity, Innate / drug effects
  • Male
  • Sequence Analysis, RNA / veterinary
  • Venereal Tumors, Veterinary / drug therapy*
  • Venereal Tumors, Veterinary / genetics
  • Vincristine / administration & dosage*
  • Vincristine / pharmacology


  • Chemokine CCL5
  • Vincristine