FoxP3+ Regulatory T-Cells in Canine Cutaneous Lymphoma and Their Role in Immune Modulation

Background/Aim: Regulatory T cells (Tregs) are immunosuppressive lymphocytes that maintain immune homeostasis but may also facilitate tumor immune evasion. Their role in canine cutaneous lymphoma (CCL) remains insufficiently understood. We hypothesized that dogs with CCL would exhibit increased Treg levels in both peripheral blood and tumor tissue, thereby contributing to local and systemic immune modulation. Our objective was to evaluate Treg levels in blood and skin of dogs with CCL compared with healthy controls. Materials and Methods: Twenty-four dogs were enrolled: 12 with T-cell cutaneous lymphoma confirmed by histopathology and immunohistochemistry and 12 clinically healthy controls, recruited from a veterinary teaching hospital population. In this prospective study, circulating Tregs were quantified by flow cytometry, and FoxP3+ cells in skin were evaluated by immunohistochemistry. Statistical analyses included t-tests, non-parametric tests, and Kaplan–Meier survival analysis. Results: Dogs with CCL had significantly higher circulating Tregs than controls (10.84±1.18% vs. 5.67±0.89%, p=0.0021). FoxP3+ cells were detected exclusively in neoplastic skin (mean, 8.27±5.71%), with no labeling in healthy skin (p=0.0007). No significant differences were observed between epitheliotropic and non-epitheliotropic subtypes. Treg levels and the Treg/CD8+ ratio were not associated with survival outcomes (p>0.20). Conclusion: Dogs with CCL demonstrated increased Tregs in both peripheral blood and intratumorally, suggesting a role of these cells in CCL-associated immunomodulation. Although Treg levels were not prognostic in this cohort, their accumulation highlights potential therapeutic targets in veterinary oncology.