Immune cell analysis in equine penile papilloma, in situ squamous cell carcinoma and invasive squamous cell carcinoma: FoxP3+ T regulatory lymphocytes differ according to equine papillomavirus 2 status.
Authors: Bacci Barbara, Martinoli Ginevra, Gallina Laura, Avallone Giancarlo, Brunetti Barbara, Franceschini Tania, Grillini Alessia, De Biase Dario, Kapetanou Athanasia, Tura Giorgia, Sarli Giuseppe, Balboni Andrea, Fiorentino Michelangelo, Ressel Lorenzo
Journal: Veterinary pathology
Summary
# Editorial Summary Equine penile tumours, particularly those associated with equine papillomavirus type 2 (EcPV2) infection, represent a significant clinical challenge, yet the immunological mechanisms underlying their development and progression remain poorly understood. Researchers examined immune cell infiltration across 27 equine penile lesions—spanning benign papillomas, in situ carcinomas, and invasive squamous cell carcinomas—using multiplex immunohistochemistry to quantify T-cells (CD3+), B-cells (CD20+), macrophages (IBA-1+), and regulatory T-cells (FoxP3+), with 18 cases confirmed EcPV2-positive by PCR and/or in situ hybridisation. Notably, whilst overall immune infiltration showed no significant variation with EcPV2 status, regulatory T-cell populations were substantially and significantly elevated in EcPV2-positive tumours in both epithelial and stromal compartments—a finding suggesting EcPV2 actively manipulates the local immune microenvironment to suppress anti-tumour responses. Additionally, macrophage density increased progressively from benign to malignant lesions, and p53 alterations correlated with malignancy markers, though neither varied by viral status. Clinically, this work indicates that EcPV2-associated tumours may evade immune recognition through regulatory T-cell enrichment, potentially explaining their aggressive behaviour and informing future immunotherapeutic strategies targeting this immunosuppressive population in affected stallions.
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Practical Takeaways
- •EcPV2-positive penile tumors show a distinct immune microenvironment characterized by higher regulatory T-cells, which may influence tumor progression and treatment response strategies
- •Histopathological assessment using Ki67 proliferation markers can help distinguish benign papillomas from malignant carcinomas, supporting clinical decision-making on treatment urgency
- •EcPV2 status should be determined in penile tumors as it may guide prognosis and inform whether immunomodulatory approaches might be beneficial in addition to surgical or other treatments
Key Findings
- •FoxP3+ regulatory T-cells were significantly more abundant in EcPV2-positive tumors compared to EcPV2-negative tumors in both intraepithelial and stromal compartments
- •IBA-1+ macrophage densities were significantly higher in squamous cell carcinomas than in papillomas or carcinomas in situ
- •Ki67 proliferation marker showed progressive increase from benign papillomas to malignant squamous cell carcinomas
- •TP53 mutations were detected in only 4/21 cases tested, with 13/21 showing wild-type TP53, and immune cell infiltrate did not vary by TP53 status