PD-L1/PD-1 and CTLA-4 Expression in Equine Penile Squamous Cell Carcinomas.
Authors: Porcellato Ilaria, Mecocci Samanta, Brachelente Chiara, Cappelli Katia, Armando Federico, Tognoloni Alessia, Chiaradia Elisabetta, Stefanetti Valentina, Mechelli Luca, Pepe Marco, Gialletti Rodolfo, Passeri Benedetta, Ghelardi Alessandro, Razzuoli Elisabetta
Journal: Animals : an open access journal from MDPI
Summary
Equine penile squamous cell carcinomas (epSCCs) are common cutaneous tumours, frequently arising from papillomavirus-induced lesions, yet treatment options remain limited. Motivated by the success of immune checkpoint inhibitors (ICIs) in human oncology, researchers used RT-qPCR and immunohistochemistry to examine PD-1/PD-L1 and CTLA-4 expression across 20 equine epithelial tumours, checkpoint pathways that regulate anti-tumour immunity. Only 3 of 20 cases expressed PD-L1 mRNA (with immunohistochemical confirmation in just one case), PD-1 was undetectable, and CTLA-4-positive cells were sparse across all samples (median 4.8 cells per high-power field). These findings suggest that PD-1/PD-L1 and CTLA-4 checkpoint pathways are minimally expressed in equine penile squamous cell carcinomas, implying that direct ICI therapy targeting these pathways may achieve limited clinical response rates in affected horses. Practitioners should be aware that whilst immunotherapy represents a conceptually appealing approach, the low immunogenicity profile of these tumours may necessitate alternative or combination strategies—highlighting the need for further investigation into other immune mechanisms or conventional treatment modalities for epSCC management.
Read the full abstract on PubMed
Practical Takeaways
- •Immune checkpoint inhibitor therapy is unlikely to be effective for equine penile squamous cell carcinomas based on low expression of targetable immune pathways in this tumor type
- •Current standard treatments for epSCCs should remain the primary approach; immunotherapy development for equine tumors should focus on other tumor types with higher immune checkpoint expression
- •Continued surveillance for EcPV2 infection and early removal of benign viral lesions remain important preventive strategies for penile tumors in horses
Key Findings
- •PD-L1 gene expression detected in only 3/20 cases (15%) by RT-qPCR; PD-1 gene not detected in any cases
- •Immunohistochemical positivity for PD-L1 found in only 1/20 cases despite some gene expression
- •CTLA-4-positive cells present in all cases but sparse, with median 4.8 cells per high power field (IQR 2.3-7.1)
- •Low expression of PD-1/PD-L1 and CTLA-4 pathways suggests immune checkpoint inhibitors may have limited efficacy in equine penile squamous cell carcinomas