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.

This study explored the relationship between the type of immune cells found in equine penile tumors and the presence of equine papillomavirus type 2 (EcPV2). Although the varieties and concentrations of B-cells, T-cells, and macrophages were same regardless of the EcPV2 status, the number of FoxP3 regulatory T-cells was significantly higher in EcPV2+ tumors.

Study Approach

• The study used multiplex immunohistochemistry (mIHC) to examine and label specific immune cell types in the tumors.
• Immunohistochemistry (IHC) was also used, a technique which visually maps the presence and location of specific proteins – in this case, FoxP3.
• This was applied to a sample of 27 horses presenting with various stages of penile tumors, from papillomas (benign warty growths) to squamous cell carcinomas (invasive, malignant growths).

Findings

• EcPV-positive tumors had more immune cell infiltrate (ICI) than EcPV-negative ones, but the difference was not statistically significant.
• However, the number of FoxP3+ (an immunosuppressive T cell) was significantly higher in EcPV2-positive tumors, suggesting a different immune response to EcPV2 infections.
• The number of IBA-1+ macrophages, another type of immune cell, was higher in the more severe squamous cell carcinomas.
• Non-basal p53 positivity (p53 is a common tumor suppressor protein) was associated with malignancy. Variants of the p53 genetic sequence were detected in a few cases.
• The study also quantified tumor proliferation using Ki67 staining, which showed a progressively higher proliferation as tumors became more malignant.

Conclusions

• In summary, the research found that, while the quantity and distribution of B-cells, T-cells, and macrophages do not change according to whether a tumor is EcPV2 positive or negative, the number of FoxP3 regulatory T-cells is significantly greater in EcPV2+ tumors.
• This work elucidates part of the complex interaction between viruses and the immune response, and provides a basis for further research. Notably, it highlights the potential role of FoxP3+ T cells in the immune response to EcPV2-positive tumors. This insight might provide targets for new therapeutic approaches.