Abstract
Background: The clinical significance and mechanistic role of immune checkpoints (ICs) in B-cell lymphoma remain underexplored. This study investigates peripheral IC expression as prognostic biomarkers and their interaction with Tregs and IL-10. Methods: Peripheral blood from 140 B-cell lymphoma patients was analyzed using flow cytometry (PD-1, CTLA-4, LAG-3, TIM-3 on CD4+/CD8+ T cells) and ELISA. Comparisons were made across disease aggressiveness, extranodal involvement, and treatment response (complete remission [CR] vs relapse/progression [R/P]). Results: Aggressive lymphomas and cases with multiple extranodal sites showed significantly elevated IC expression (all p < 0.05). R/P patients demonstrated markedly higher PD-1 expression (CD4+: 26.1% vs 8.2%; CD8+: 25.2% vs 7.1%; p < 0.001) and elevated CTLA-4, LAG-3, TIM-3 versus CR patients. PD-1 and CTLA-4 showed significant prognostic value (AUC > 0.7), unlike LAG-3/TIM-3. R/P patients had increased Treg proportions (7.84% vs 3.58%, P<0.0001) and IL-10 levels (10.5 vs 5.44 pg/mL, p < 0.0001). PD-1 on CD4+ T cells correlated positively with Treg frequency (r = 0.539, p < 0.0001) and IL-10 levels (r = 0.457, p < 0.0001). Conclusion: Peripheral T-cell ICs, particularly PD-1 and CTLA-4, are significant prognostic biomarkers in B-cell lymphoma. The correlation between PD-1+ CD4+ T cells, Treg expansion, and IL-10 elevation is consistent with a mechanism whereby PD-1 signaling may contribute to immunosuppression through Treg differentiation and JAK2/STAT3 pathway activation, providing insights for therapeutic targeting.