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

Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor.

Author information

1
Department of Infection, Division of Infection & Immunity, University College London (UCL), Cruciform Building, 90 Gower Street, London WC1E 6BT, UK.
2
Department of Veterinary Sciences, Polo Universitario dell'Annunziata, University of Messina, Messina 98168, Italy.
3
Department of Cancer Biology, Cancer Institute, UCL, 72 Huntley Street, London WC1E 6BT, UK.
4
MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London WC1E 6BT, UK.
5
Transmissible Cancer Group, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
6
Department of Infection, Division of Infection & Immunity, University College London (UCL), Cruciform Building, 90 Gower Street, London WC1E 6BT, UK. Electronic address: a.fassati@ucl.ac.uk.

Abstract

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

PMID:
29634949
PMCID:
PMC5896242
DOI:
10.1016/j.ccell.2018.03.003
[Indexed for MEDLINE]
Free PMC Article

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