Effects of Interferon on PD-1/PD-L1 and Treg Expression in JAK2 V617F-positive Myeloproliferative Neoplasms

Objective To explore the effect of interferon-alpha-2b(IFN-alpha 2b) on the expression of programmed death receptor-1(PD-1), programmed death ligand-1(PD-L1) and CD4⁺ CD25⁺ Foxp3⁺ regulatory T cell (Treg) in JAK2 V617F-positive myeloproliferative neoplasms(MPN) and related clinical significance.

Methods We collected 61 cases of JAK2 V617F-positive MPN patients, including 41 cases as the newly diagnosed group, 20 cases as the IFN-α2b treatment group and 20 healthy volunteers as control group. JAK2 V617F/JAK2 ratio was detected by fluorescence quantitative polymerase chain reaction (FQ-PCR). The expression levels of PD-1 and PD-L1 in bone marrow and Treg in peripheral blood were detected by flow cytometry. The bone marrow and peripheral blood samples from 15 patients were selected and treated with 1×10⁶U/L IFN-α2b for 48h; and then the expression levels of PD-1, PD-L1 and Treg were detected.

Results The expression levels of JAK2 V617F, PD-1, PD-L1 and Treg in the newly diagnosed group were significantly higher than those in IFN-α2b treatment group and control group(P < 0.05). The expression levels of PD-1, PD-L1 and Treg in the patients with JAK2 V617F/JAK2 ratio≥50% were significantly higher than those with mutation rate < 50%(P < 0.05). JAK2 V617F burden was positively correlated with PD-1, PD-L1 in bone marrow and PD-1 in lymphocyte, while not correlated with Treg. The expression of PD-1, PD-L1 and Treg in primary MPN cells were inhibited by IFN-α2b after 48 hours(P < 0.05).

Conclusion PD-1, PD-L1 and Treg participate in the pathogenesis of MPN together. Interferon could inhibit the progress of MPN via inhibiting the expression of JAK2 V617F, PD-1, PD-L1 and Treg.