背景:在小鼠模型中已经描述了具有JAK2-V617F突变的骨髓增殖性肿瘤(MPN)在巨核细胞中程序性死亡配体1(PD-L1)的表达增加,从而通过抑制T淋巴细胞导致癌症免疫逃避。
目的:为了量化和比较MPNJAK2阳性患者骨髓(BM)的PD-L1表达,负,正常控制。
方法:我们收集了MPNJAK2阳性患者的BM,1990年至2019年的阴性和正常对照。我们还创建了一个评分系统来量化巨核细胞中的PD-L1表达。
结果:我们获得了14个BM,JAK2阳性PMF,5JAK2负PMF,10例BM活检正常的患者。与对照组相比,JAK2阳性组的PD-L1表达更高,得分为212.6和121.1(t值2.05,p值0.025)。此外,无论JAK2突变状态如何,PMF组的评分均高于对照组,分别为205.9和121.1(t值2.12,p值0.021).JAK2阴性组与对照组187.2和121.1之间的PD-L1评分没有差异(t值1.02,p值0.162)。
结论:这些发现表明,与对照组相比,具有JAK2突变的PMF患者在巨核细胞中具有更高的PD-L1表达。我们推测,考虑到较高的PD-L1表达,检查点和JAK2抑制剂的组合可能是JAK2突变的PMF的积极治疗选择。
BACKGROUND: It has been described in mice models that myeloproliferative neoplasm (MPN) with JAK2-V617F mutation has an increased expression of programmed death-ligand 1 (PD-L1) in megakaryocytes leading to cancer immune evasion by inhibiting the T-lymphocytes.
OBJECTIVE: To quantify and compare the PD-L1 expression on bone marrow (BM) of patients with MPN JAK2 positive, negative, and normal controls.
METHODS: We collected BM of patients with MPN JAK2 positive, negative and normal controls from 1990 to 2019. We also created a scoring system to quantify PD-L1 expression in megakaryocytes.
RESULTS: We obtained 14 BM with JAK2 positive PMF, 5 JAK2 negative PMF, and 10 patients with normal BM biopsies. PD-L1 expression was higher in the JAK2 positive group compared with the control group with a score of 212.6 versus 121.1 (t-value 2.05, p-value 0.025). In addition, the score was higher in the PMF group regardless of JAK2 mutational status when compared with the control group with score of 205.9 versus 121.1 (t-value 2.12, p-value 0.021). There was no difference in the PD-L1 score between the JAK2 negative versus the control group 187.2 versus 121.1 (t-value 1.02, p-value 0.162).
CONCLUSIONS: These findings suggest that PMF patients with a JAK2 mutation have a higher PD-L1 expression in megakaryocytes compared with the control group. We postulate that the combination of checkpoint and JAK2 inhibitors may be an active treatment option in JAK2 mutated PMF given the higher PD-L1 expression.