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

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Abstract

Purpose

The  PD-1 (programmed cell death-1) receptor is expressed on the surface of activated T cells. Its ligand, programmed 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.

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Availability of data and material

The data that support the findings of this study are available from the corresponding author, [G M], upon request.

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Acknowledgements

Authors would like to thank all the patients and their families for participating in this project. They also acknowledge the team of the Molecular Biology Research Lab in the Medical Research Center of Alexandria Faculty of Medicine.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Clinical Pathology Department, Faculty of Medicine, University of Alexandria, Alexandria, Egypt

    M. A. Gamaleldin & R. A. Abo Elwafa

  2. Internal Medicine Department (Hematology Unit), Faculty of Medicine, University of Alexandria, Alexandria, Egypt

    O. M. Ghallab & E. A. Nadwan

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  1. M. A. Gamaleldin
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  2. O. M. Ghallab
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  3. E. A. Nadwan
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  4. R. A. Abo Elwafa
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Correspondence to M. A. Gamaleldin.

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The study was conducted after approval of the Medical Ethics Committee of Alexandria Faculty of Medicine.

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Gamaleldin, M.A., Ghallab, O.M., Nadwan, E.A. et al. PD-1 and PD-L1 gene expressions and their association with Epstein-Barr virus infection in chronic lymphocytic leukemia. Clin Transl Oncol 23, 2309–2322 (2021). https://doi.org/10.1007/s12094-021-02657-y

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