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.

Keywords: Lymphoproliferative neoplasms; Programmed death ligand 1; Programmed cell death protein 1; C-X-C motif chemokine receptor 3; Systemic immune inflammation index; Systemic inflammation response index; Inflammatory biomarkers

Core Tip: This case-control study explores the prognostic value of programmed death-ligand 1/programmed cell death protein 1 co-expression and C-X-C motif chemokine receptor 3 (CXCR3)-driven immune signatures in Egyptian patients with lymphoproliferative neoplasms. By integrating flow cytometry analysis with systemic inflammation indices (systemic immune-inflammation index and systemic inflammation response index), the study identifies novel biomarker panels predictive of disease stage, recurrence, and survival. Findings support the use of programmed death-ligand 1/CXCR3 and programmed cell death protein 1/CXCR3 as clinically relevant tools for risk stratification in resource-limited settings, paving the way for the personalized management of lymphoproliferative neoplasms.