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. 2025 Jul 3;63(11):2318-2329.
doi: 10.1515/cclm-2025-0306. Print 2025 Oct 27.

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

Christoph Winkler  1 , Markus Anliker  1 , Stefan Schmidt  2 , Clemens Feistritzer  2 , Britta Höchsmann  3   4 , Hubert Schrezenmeier  3   4 , Anita Siller  5 , Andrea Griesmacher  1 , Lorin Loacker  1
Affiliations

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

Christoph Winkler et al. Clin Chem Lab Med. .

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: CTLA-4; JAK2; PD-1; PD-L1; immune checkpoints; myeloproliferative disorders.

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