Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Dan Frampton, Hagen Schwenzer, Gabriele Marino, Lee M. Butcher, Gabriele Pollara, Janos Kriston-Vizi, Cristina Venturini, Rachel Austin, Karina Ferreira de Castro, Robin Ketteler, Benjamin Chain, Richard A. Goldstein, Robin A. Weiss, Stephan Beck, Ariberto Fassati
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.

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Teaser

By analyzing serial biopsies of vincristine-treated canine transmissible venereal tumors, Frampton et al. show that tumor regression occurs in sequential steps involving the activation of the innate immune system and immune infiltration of the tumor, and they identify CCL5 as a possible driver of regression.


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