Prognostic Impact of FoxP3 and PD1 Expression in the Tumor Microenvironment (TME) of Classical Hodgkin Lymphoma (cHL)

Background: FoxP3 and programmed cell death protein 1 (PD-1) are immunoregulatory markers involved in the tumor microenvironment (TME) of Hodgkin lymphoma. Their prognostic significance in classical Hodgkin lymphoma (cHL) remains controversial. Objective: This study aimed to evaluate the prognostic significance of FoxP3- and PD-1-positive immune cells in cHL patients in an Ethiopian cohort. Methods: Clinical records of 68 consecutive patients diagnosed with cHL between 2015 and 2019 were retrospectively reviewed, with follow-up for up to 9 years. Tissue microarray sections were stained for FoxP3 and PD-1 by immunohistochemistry, and positive immune cells were quantified using HALO 2.3 digital image analysis. Overall survival (OS) and event-free survival (EFS) were assessed using Kaplan–Meier analysis and Cox proportional hazards regression. Results: The 5-year overall survival (OS) and event-free survival (EFS) rates were 82.8% and 79.9%, respectively, while the corresponding 9-year rates were 78.6% and 66.5%. Patients in the high-risk International Prognostic Score (IPS) group had lower 9-year OS and EFS rates of 63.5% and 41.4%, respectively (P = 0.04). Low lymphocyte count (≤0.6 × 10⁹/L) was associated with inferior OS (HR=10.9; 95% CI: 1.4–84.0; P=0.016) and EFS (HR=5.9; 95% CI: 1.7–20.0; P=0.005). High FoxP3 expression (≥9%) and high PD-1 expression (≥24.6%) were associated with poorer OS, with HRs of 4.3 (95% CI: 1.2–15.7; P=0.020) and 3.4 (95% CI: 1.2–15.7; P=0.030), respectively. High-risk IPS (≥3) was associated with inferior OS and EFS (P=0.04). In multivariable analysis, low lymphocyte count, high FoxP3, and high PD-1 remained significantly associated with poorer OS. Conclusions: High FoxP3 and PD-1 expression, and low lymphocyte count were associated with unfavorable outcomes. FoxP3 and PD-1 warrant further validation as potential prognostic biomarkers in cHL.