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Cellular expression of PD-1, PD-L1 and CTLA-4 in patients with JAK2V617F mutated myeloproliferative disorders

  • Christoph Winkler , Markus Anliker , Stefan Schmidt , Clemens Feistritzer , Britta Höchsmann , Hubert Schrezenmeier , Anita Siller , Andrea Griesmacher and Lorin Loacker ORCID logo EMAIL logo
Published/Copyright: July 3, 2025
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 11

Abstract

Objectives

The acquired, somatic JAK2V617F mutation is the most common molecular aberration in patients with myeloproliferative neoplasms (MPN) and also significantly involved in the regulation of T cell immunity. PD-1, PD-L1 and CTLA-4 are key immune checkpoint regulators that are elevated in patients with solid tumors, infectious diseases and chronic inflammation. We aimed further investigating the significance of immune checkpoint expression in JAK2V617F positive MPN.

Methods

The surface expression of PD-L1, PD-1 and CTLA-4 on peripheral blood leukocytes was determined by flow cytometry in 27 patients with JAK2V617F positive MPN and in a control group of 26 healthy individuals and analyzed by immune checkpoint and leukocyte subpopulation. In addition, the concentration of soluble PD-L1 (sPD-L1) in plasma was examined by ELISA.

Results

PD-1, PD-L1 and CTLA-4 are significantly overexpressed on the surface of granulocytes in JAK2 positive patients compared to the control group. Soluble PD-L1 (sPD-L1) is elevated in the plasma of JAK2 positive patients and increases with decreased renal function. In CD8+ T-cells and CD4+ T-cells there is a significant negative correlation between PD-1 expression or sPD-L1 concentration and their corresponding cell count.

Conclusions

Our study shows a significant increase of immune checkpoint regulators on the cellular surface as well as soluble PD-L1 in JAK2 mutated patients compared to healthy individuals. Increased activation of the JAK2/STAT signaling pathway by JAK2V617F appears to be a mechanism of reduced immune activation in patients with MPN. Immune checkpoint inhibition might therefore represent a potential additional therapeutic target in this disease group.

Keywords: PD-1; PD-L1; CTLA-4; myeloproliferative disorders; JAK2; immune checkpoints
Corresponding author: Lorin Loacker, Central Institute of Clinical and Chemical Laboratory Diagnostics, University Hospital of Innsbruck, Anichstr. 35, Innsbruck, Austria, E-mail:

Acknowledgments

The authors acknowledge the technical assistance of Isabella Staubmann, Margit Lanthaler, Christopher Geiger and their colleagues of the Central Institute of Clinical and Chemical Laboratory Diagnostics, University Hospital of Innsbruck, Innsbruck, Austria and Dr. Inge von Zabern for fruitful discussions on this topic and proofreading of the manuscript.

  1. Research ethics: Ethics Committee approval from the Medical University of Innsbruck (1176/2019) was obtained.

  2. Informed consent: Informed consent was obtained from all individuals included in this study.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0306).

Received: 2025-03-13
Accepted: 2025-06-12
Published Online: 2025-07-03
Published in Print: 2025-10-27

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2025-0306
Keywords for this article
PD-1; PD-L1; CTLA-4; myeloproliferative disorders; JAK2; immune checkpoints

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  1. Frontmatter
  2. Editorial
  3. Advancing diagnostic stewardship through claims-based utilization analysis: toward a system-wide vision of diagnostic excellence
  4. Review
  5. Biomarkers in body fluids and their detection techniques for human intestinal permeability assessment
  6. Mini Review
  7. Challenges of using natriuretic peptides to screen for the risk of developing heart failure in patients with diabetes: a report from the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Committee on Clinical Applications of Cardiac Bio-Markers (C-CB)
  8. Opinion Papers
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  14. Utilization analysis of laboratory tests using health insurance claims data: advancing nationwide diagnostic stewardship monitoring systems
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  21. Investigation of the possible cause of over-estimation of human aldosterone in plasma, using a unique, non-synthetic human aldosterone-free matrix
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