Interplay of PD-L1, FOXP3, and CD8 in the Immune Microenvironment of Penile Squamous Cell Carcinoma: Expression Profiles and Correlations.

Background

This study investigates the interplay between PD-L1, FOXP3+ regulatory T cells, and CD8+ cytotoxic T lymphocytes in penile squamous cell carcinoma (penile SCC), where understanding the tumor immune microenvironment is crucial.

Methods

We analyzed 108 penile SCC specimens using tissue microarrays (528 spots). Immunohistochemistry was performed for PD-L1, FOXP3, and CD8. Expression was quantified in tumor and stromal compartments, and correlated with clinicopathological features including histological grade, HPV-associated morphology, and host inflammatory response.

Results

PD-L1 in tumor cells positively correlated with intratumoral CD8+ (rho = 0.408, P < .001) and FOXP3+ T cells (rho = 0.293, P = .009). Peritumoral FOXP3+ and CD8+ T cells also showed a strong correlation (rho = 0.753, P < .001). Higher PD-L1 and intratumoral CD8+ were associated with higher histological grade (P < .001). HPV-associated morphology correlated with higher PD-L1 (P < .001) but lower FOXP3+ infiltration (P < .001). Intense inflammatory response was associated with increased peritumoral FOXP3+ and CD8+ T cells (P < .001).

Conclusions

The immune microenvironment of penile SCC involves complex interactions among PD-L1, FOXP3+, and CD8+, and was significantly influenced by histological grade, HPV status, and inflammation. The strong co-localization of peritumoral regulatory and cytotoxic T cells suggests a critical regulatory axis. These findings highlight distinct immune profiles within penile SCC, offering insights for developing tailored immunotherapeutic strategies.