Background: Penile squamous cell carcinoma (PSCC) presents significant challenges in diagnosis and treatment. Understanding the complex immunological landscape, particularly the interaction between PD-L1, FOXP3, and CD8, is crucial for developing effective therapeutic strategies. Methods: We analyzed 108 PSCC cases through 528 tissue microarray samples. Immunohistochemical staining was performed using standardized protocols to detect PD-L1, FOXP3, and CD8 expression. Expression patterns were evaluated in both tumor and stromal compartments, with assessment of membranous staining for PD-L1 and quantification of FOXP3+ and CD8+ lymphocytes. Results: PD-L1 expression in tumor cells showed a moderate positive correlation (r=0.477, P<0.001) with CD8+ T-cell infiltration in the tumor compartment, suggesting an adaptive immune resistance mechanism. PD-L1 expression in tumor cells demonstrated a weak positive correlation (r=0.289, P=0.002) with FOXP3 expression in tumor-associated lymphocytes. The strongest correlation observed (r=0.717, P<0.001) was between FOXP3 expression in stromal lymphocytes and CD8+ T-cell presence in stromal areas. PD-L1 expression in lymphocytes showed a significant correlation (r=0.354, P<0.001) with FOXP3 expression in stromal lymphocytes. Conclusions: Our findings reveal complex interactions between PD-L1, FOXP3, and CD8 within the tumor microenvironment of PSCC. The strong correlation between stromal FOXP3+ and CD8+ cells points to a crucial immune regulatory axis that could influence treatment outcomes. These results provide insights for developing targeted therapeutic strategies and improving patient care in PSCC.

The authors have declared no competing interest.

This study did not receive any funding.

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The Institutional Review Board at the Johns Hopkins School of Medicine (Baltimore, MD) gave ethical approval for this work.

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