Effects of Interferon on PD-1/PD-L1 and Treg Expression in JAK2 V617F-positive Myeloproliferative Neoplasms
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摘要:目的
探讨干扰素-alpha-2b（IFN-α2b）对JAK2 V617F阳性骨髓增殖性肿瘤（MPN）患者中程序性死亡受体-1（PD-1）、程序性死亡配体-1（PD-L1）及CD4+ CD25+ Foxp3+调节性T细胞（Treg）表达的影响及临床意义。
方法收集JAK2 V617F阳性MPN患者61例，包括初治组41例、IFN-α2b治疗组20例，健康对照组20例。应用荧光定量PCR检测JAK2 V617F/JAK2突变率，流式细胞术检测PD-1、PD-L1、Treg的表达情况。选取15例患者骨髓及外周血标本进行体外细胞培养，应用1×106 U/L IFN-α2b作用48 h后检测PD-1、PD-L1及Treg表达情况。
结果初治组的JAK2 V617F、PD-1、PD-L1及Treg表达明显高于IFN-α2b治疗组及对照组（均P < 0.05）。JAK2 V617F突变量≥50%患者骨髓髓系细胞PD-1、PD-L1及外周血Treg细胞均明显高于突变量 < 50%患者（均P < 0.05）。相关性分析结果显示JAK2 V617F突变量与骨髓髓系细胞PD-1、PD-L1和淋巴细胞PD-1呈正相关，与Treg表达无相关性。1×106 U/L IFN-α2b作用48 h后能够体外抑制MPN原代细胞PD-1、PD-L1及Treg的表达（P < 0.05）。
结论PD-1、PD-L1及Treg共同参与了MPN的发病过程，干扰素能够不同程度抑制MPN JAK2 V617F、PD-1、PD-L1及Treg表达，进而抑制MPN的进展。
Abstract:ObjectiveTo 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.
MethodsWe 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.
ResultsThe 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).
ConclusionPD-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.
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Key words:
- PD-1 /
- PD-L-1 /
- Treg /
- Myeloproliferative neoplasms(MPN) /
- Interferon
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作者贡献张丽军：负责文章的数据统计、撰写、修改工作; 齐峰、成志勇、梁文同：导师组成员，负责课题的构思及设计工作; 张朝、吴士杰：负责流式细胞学实验部分; 郭艳涛、孙丽娜、彭占仙：负责收集病例及数据采集工作
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图 1 PD-1、PD-L1在JAK2 V617F阳性骨髓增殖性肿瘤初治组和健康对照组中的表达情况
Figure 1 Expression of PD-1 and PD-L1 in control group and newly diagnosed group of JAK2 V617F-positive myeloproliferative neoplasms
表 1 JAK2 V617F阳性骨髓增殖性肿瘤不同组JAK2 V617F、PD-1、PD-L1及Treg表达量的关系(x±s)
Table 1 Expression of JAK2 V617F, PD-1, PD-L1 and Treg in different groups of JAK2 V617F-positive myeloproliferative neoplasms (x±s)
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表 2 JAK2 V617F突变量与PD-1、PD-L1及Treg的表达的关系(x±s)
Table 2 Relationship between JAK2 V617F and expression of PD-1, PD-L1 and Treg (x±s)
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表 3 IFN-α2b作用前后髓系细胞PD-1、PD-L1，淋巴细胞PD-1及Treg表达量的比较(x±s)
Table 3 Comparison of PD-1, PD-L1 expressions in myeloid cells, PD-1 expression in lymphocyte, Treg expression before and after IFN-α2b treatment (x±s)
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