PD‑1 and PD‑L1 gene expressions and their association with Epstein‑Barr virus infection in chronic lymphocytic leukemia

• Autores: M.A. Gamaleldin, O. Ghallab, E.A. Nadwan, R.A. Abo Elwafa
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 23, Nº. 11, 2021, págs. 2309-2322
• Idioma: inglés
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• Resumen

  • Purpose The PD-1 (programmed cell death-1) receptor is expressed on the surface of activated T cells. Its ligand, pro- grammed cell death ligand-1 (PD-L1), is expressed on the surface of dendritic cells or macrophages. The PD-1/PD-L1 interaction ensures prevention of autoimmunity by activating the immune system only when needed. In cancers, PD-L1 expressed on the tumour cells binds to PD-1 receptors on the activated T cells, leading to inhibition of the cytotoxic T cells and immunosuppression. PD-1/PD-L1 pathway is upregulated in EBV infection that is known to worsen the CLL prognosis.

    Therefore, we aimed to study the association between PD-1 and PD-L1 expressions, EBV status and the CLL prognosis.

    Methods and patients The study was conducted on 80 newly diagnosed CLL patients and 80 controls. We analyzed PD-1 and PD-L1 expressions and EBV-DNA load by real-time PCR. The cytogenetic abnormalities and expression of ZAP70 and CD38 were detected by FISH and Flow cytometry, respectively.

    Results PD-1/PD-L1 expressions were significantly upregulated in CLL patients compared to controls. In addition, their mRNA levels were significantly higher in EBV( +) versus EBV( −) patients. High expression of PD-1/PD-L1 was associated with poor prognostic markers (RAI stages of CLL, del 17p13, ZAP70, and CD38 expression), failure of complete remission, shorter progression-free survival, and overall survival.

    Conclusion High expression of PD-1 and PD-L1, together with high EBD-DNA load were linked to worse prognosis in CLL. In addition, PD-1 and PD-L1 might represent suitable therapeutic targets for patients suffering from aggressive CLL.