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Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor

Dan Frampton1, Hagen Schwenzer1, Gabriele Marino2

  • 1Department of Infection, Division of Infection & Immunity, University College London (UCL), Cruciform Building, 90 Gower Street, London WC1E 6BT, UK.

Cancer Cell
|April 11, 2018
PubMed

Insights

The canine transmissible venereal tumor (CTVT) undergoes regression through distinct stages, driven by the host

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Canine transmissible venereal tumor (CTVT) is a unique contagious cancer.
  • CTVT undergoes spontaneous or treatment-induced regression.
  • Mechanisms underlying CTVT regression remain largely unknown.

Purpose of the Study:

  • To elucidate the molecular and cellular mechanisms of CTVT regression following vincristine treatment.
  • To identify key biological pathways and molecules involved in tumor regression.

Main Methods:

  • Global transcriptional profiling of serial CTVT biopsies.
  • Methylation analysis of serial CTVT biopsies.
  • Functional pathway analysis.

Main Results:

  • CTVT regression occurs in sequential steps: innate immune activation, epithelial remodeling, immune infiltration, cell cycle arrest, and tissue repair.
  • CCL5 identified as a potential driver of CTVT regression.
  • Gene expression changes correlate with intragenic methylation alterations.

Conclusions:

  • Host innate immunity plays a critical role in initiating CTVT regression.
  • A multi-step process involving immune and tissue remodeling underlies tumor regression.
  • CCL5 is a potential therapeutic target for promoting cancer regression.
Keywords:
CCL5cancerdogepithelialinnate immunitymelanomamethylationregressiontransmissiblevincristine

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