Objective To study the changes of programmed death factor-1/programmed death factor-1 ligand (PD-1/PD-L1) in patients with myelodysplastic syndrome (MDS) before and after using decitabine (DAC). Methods From Jan 2016 to Jan 2017, 18 cases newly diagnosed as MDS with WHO 2008 type WPSS prognostic stratification in middle-risk group and high-risk group were enrolled. Patients were applied with DAC (20 mg/m2 d1-d5, 21-28 days as a cycle) for 2 cycles. Five patients with non-malignant hematologic diseases were treated as control. Peripheral blood and bone marrow cells were collected before and after DAC application for 2 cycles. FCM was used to determine PD-1 of CD3+CD4+T and CD3+CD8+T cells in peripheral blood lymphocytes and PD-L1 in bone marrow progenitor cells before and after treatment with DAC. The relative expression of PD-lmRNA and PD-LlmRNA in peripheral blood and bone marrow mononuclear cells before and after DAC treatment was detected by QPCR. PD-1/PD-L1 level was compared between remission group (n= 5 ) and non-remission group (n = 13). Results FCM analysis showed that the proportion of PD-1of CD3 + CD4+T and CD3+CD8+T lymphocytes, and PD-L1 of bone marrow monounclear cells in middle-risk group after DAC treatment was(11.43±1.88)％,(11.46±1.60)％ and (16.59±0.72)％, and the data in high-risk group after treatment were (16.36±3.71)％,(16.59±3.81)％ and (18.69±1.60)％,all higher than those before treatment and those of control group (P<0.05). The proportion of PD-1 of CD3+CD4+T and CD3 + CD8+T lymphocytes, and PD-L1 of bone marrow mononuclear cells in non-remission group was(18.51±2.62)％, (19.03±2.18)％ and (19.22±1.40) ％,higher than those in remission group (P<0.05). QPCR analysis showed that after DAC treatment the relative expression of PD-1 mRNA in peripheral blood and PD-L1 mRNA in bone marrow mononuclear cells of middle-risk group was 6.32±3.37 and 2.88±1.72, and they were 12.55±6.27 and 7.47±4.90 in high risk group, higher than those before treatment (P<0.05). The relative expression of PD-1 mRNA of peripheral blood mononuclear cells and PD-L1 mRNA of bone marrow mononuclear cells in non-remission group was 16.28±4.64 and 9.16±5.40, significantly higher than those in remission group (P<0.05). Conclusion After treatment with DAC, the expression of PD-1/PD-L1 in peripheral blood and bone marrow of MDS middle-risk, high-risk patients increased significantly, especially in non-remission group. High expression of PD-1/PD-L1 may be one of the reasons leading to drug resistance of DAC.%目的探讨骨髓增生异常综合征(MDS)患者接受地西他滨(DAC)治疗前后程序性死亡因子-1/程序性死亡因子-1配体(PD-1/PD-L1)的变化.方法收集2016年1月至2017年1月初治MDS中符合WHO 2008分型WPSS预后分层中危组及高危组并接受DAC(20 mg/m2 d1 ～d5,21～28天为1个周期,治疗2个周期)治疗的18例患者,同时以5例非恶性血液病患者为对照.于DAC治疗前后收集外周血和骨髓细胞.流式细胞术(FCM)检测DAC治疗前后外周血CD3+CD4+T、 CD3+CD8+T淋巴细胞的PD-1和骨髓单核细胞PD-L1的变化;QPCR检测DAC治疗前后外周血及骨髓单个核细胞PD-1 mR-NA、PD-L1 mRNA相对表达量的变化;比较化疗缓解组(n=5)和未缓解组(n=13)PD-1/PD-L1的表达水平.结果FCM检测显示,DAC治疗后,中危组CD3 + CD4+T、CD3 + CD8+T淋巴细胞PD-1和骨髓单个核细胞的PD-L1比例分别为(11.43±1.88)％、(11.46±1.60)％和(16.59±0.72)％,高危组分别为(16.36±3.71)％、(16.59±3.81)％和(18.69±1. 60)％,均高于治疗前和对照组(P<0.05);未缓解组CD3+CD4+T、CD3 + CD8+T淋巴细胞PD-1和骨髓单个核细胞上PD-L1的比例分别为(18.51±2.62)％和(19.03±2.18)％和(19.22±1.40)％,高于缓解组(P<0.05).QPCR检测显示,DAC治疗后,中危组外周血单个核细胞PD-1 mRNA和骨髓单个核细胞PD-L1 mRNA的相对表达量为6.32±3.37和2.88±1.72,高危组分别为12. 55±6.27和7.47±4.90,均高于治疗前(P<0.05).MDS未缓解组外周血PD-1 mRNA和骨髓单个核细胞PD-L1 mRNA的相对表达为16.28±4.64和9.16±5.40,高于缓解组(P<0.05).结论DAC治疗后中、高危MDS患者的外周血、骨髓中PD-1/PD-L1表达明显上升,尤其是未缓解组,PD-1/PD-L1高表达可能是介导DAC耐药的原因之一.
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