Canine Transmissible Venereal Tumour: A Natural Model of Immune Evasion in Comparative Oncology.

Abstract

Canine transmissible venereal tumour (CTVT) is the oldest naturally occurring transmissible cancer and serves as a unique comparative model for tumour-immune interactions. Unlike conventional neoplasms, CTVT is transmitted as an allograft between genetically distinct hosts, facing strong immune pressure while maintaining clonal persistence for millennia. This success reflects its remarkable ability to evade, adapt to, and remodel host immunity. CTVT modulates the tumour microenvironment through secretion of immunosuppressive cytokines such as TGF-β and IL-10, downregulation of MHC molecules, impaired dendritic cell differentiation, and disrupted apoptotic signalling. IL-8 further contributes by shifting the immune profile from Th1 to Th2 and inducing neutrophil extracellular traps (NETs), which promote antigen sequestration, angiogenesis, stromal remodelling, and dissemination. Immunometabolic reprogramming, including lactate-driven suppression of cytotoxic lymphocytes and NK cells, reinforces immune escape. Molecular pathways central to human oncology-such as STAT3, FGFR, PPAR-γ, and p53-remain underexplored in CTVT but may critically shape its immune dynamics. Recent findings indicate synonymous TP53 mutations associated with reduced p53 expression, partial apoptotic activation through caspase-9, and overexpression of BCL2, BAX, and MMP-9, highlighting imbalance between cell death regulation and extracellular matrix remodelling. The alternation between progressive and regressive phases provides a natural framework to study tumour immunoediting, tolerance, and long-term dormancy. Beyond its biological relevance, CTVT functions as a natural transplantation model in immunocompetent hosts and a platform for immunotherapeutic approaches, including dendritic cell-based vaccines. Altogether, the evolutionary longevity, genetic adaptability, and immune plasticity of CTVT underscore its value for comparative oncology and the development of novel immunotherapies.