Prognostic significance of PD-L1/PD-1 co-expression and CXCR3-driven inflammatory signatures in Egyptian patients with lymphoproliferative neoplasms

Abstract

BACKGROUND: Lymphoproliferative neoplasms (LPNs) such as chronic lymphocytic leukemia and non-Hodgkin lymphomas are clinically heterogeneous and frequently associated with recurrence and poor outcomes. Immune checkpoint markers, including programmed death-ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1), as well as C-X-C motif chemokine receptor 3 (CXCR3) and inflammation-based indices [systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI)], have shown promise in risk stratification but remain underexplored in Egyptian populations. AIM: To assess the prognostic value of PD-L1/PD-1 co-expression with CXCR3, SII, SIRI, and CXCR3 expression on monocyte subsets and lymphocytes in Egyptian patients with LPNs. METHODS: A case-control study was conducted at Kafr Elsheikh University Hospitals (January 2024 to January 2025), including 90 patients with LPNs (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma) and 90 matched healthy controls. All participants underwent clinical evaluation, laboratory testing (including complete blood count, C-reactive protein, lactate dehydrogenase, and ferritin), and flow cytometry for PD-L1, PD-1, and CXCR3. Inflammatory indices (SII, SIRI, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and ferritin-to-lymphocyte ratio) were calculated. Clinical outcomes included remission, recurrence, and survival. RESULTS: Patients with LPNs had marked hematological and biochemical alterations, including anemia, thrombocytopenia, and reduced neutrophils, with significantly elevated lactate dehydrogenase, C-reactive protein, ferritin, and systemic inflammatory indices (SII, SIRI). Inflammatory ratios (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio) were lower, whereas the ferritin-to-lymphocyte ratio was higher compared with controls. Immune profiling showed significantly increased PD-L1/CXCR3 and PD-1/CXCR3 co-expression and higher CXCR3 expression on T lymphocytes. Post-treatment, PD-L1/CXCR3, CXCR3/T lymphocyte expression, SII, and SIRI decreased. Prognostic evaluation revealed that SIRI, PD-L1/CXCR3, and PD-1/CXCR3 had high accuracy for identifying stage IV disease, with patients showing low baseline levels achieving superior survival (100% follow-up). Clinically, 21.1% achieved complete remission, 26.7% relapsed, and 15.6% died. CONCLUSION: PD-L1/PD-1 co-expression with CXCR3, combined with SII and SIRI, constitutes a practical prognostic panel for staging and outcome prediction in Egyptian patients with LPNs. These biomarkers may guide personalized management and therapeutic monitoring.