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Peer-reviewedCC BY-NC-ND 4.0In Vivo

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

5 affiliations
  1. 1Department of Veterinary Clinical and Surgery, São Paulo State University, Jaboticabal, SP, Brazil
  2. 2Oncospes e Onconnectionvet, Ribeirão Preto, SP, Brazil
  3. 3Centro Universitário Barão de Mauá - Campus Veterinário, Ribeirão Preto, SP, Brazil
  4. 4Department of Veterinary Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo – USP, São Paulo, SP, Brazil
  5. 5Department of Veterinary Surgery and Animal Science, School of Veterinary Medicine and Animal Science, São Paulo State University – UNESP, Botucatu, SP, Brazil

Abstract

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.

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BibTeX
@article{semolin2026foxp3,
  title = {{FoxP3+ Regulatory T-Cells in Canine Cutaneous Lymphoma and Their Role in Immune Modulation}},
  author = {LÍVIA MARIA SOUZA SEMOLIN and LETÍCIA ABRAHÃO ANAI and PAULO CÉSAR JARK and THIAGO DEMARCHI MUNHOZ and GIOVANNA GABRIELLE CRUVINEL and RAFAEL COSTA BITENCOURT and MÁRCIA FERREIRA DA ROSA SOBREIRA and ANNELISE CARLA CAMPLESI and JULIANA RODRIGUES LEITÃO and AUREO EVANGELISTA SANTANA and CARLOS EDUARDO FONSECA ALVES},
  journal = {In Vivo},
  year = {2026},
  month = oct,
  doi = {10.21873/invivo.14500},
  url = {https://doi.org/10.21873/invivo.14500},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - FoxP3+ Regulatory T-Cells in Canine Cutaneous Lymphoma and Their Role in Immune Modulation
AU  - LÍVIA MARIA SOUZA SEMOLIN
AU  - LETÍCIA ABRAHÃO ANAI
AU  - PAULO CÉSAR JARK
AU  - THIAGO DEMARCHI MUNHOZ
AU  - GIOVANNA GABRIELLE CRUVINEL
AU  - RAFAEL COSTA BITENCOURT
AU  - MÁRCIA FERREIRA DA ROSA SOBREIRA
AU  - ANNELISE CARLA CAMPLESI
AU  - JULIANA RODRIGUES LEITÃO
AU  - AUREO EVANGELISTA SANTANA
AU  - CARLOS EDUARDO FONSECA ALVES
PY  - 2026
DA  - 2026/10/29
JO  - In Vivo
DO  - 10.21873/invivo.14500
UR  - https://doi.org/10.21873/invivo.14500
AB  - 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.
SN  - 0258-851X
SN  - 1791-7549
ER  -