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[α-1b干扰素、白细胞介素-2与沙利度胺对急性髓系白血病患者免疫调节的协同机制]

[Synergistic Mechanism of Interferon alpha-1b, Interleukin-2 and Thalidomide for Immune Regulation in Patients with Acute Myeloid Leukemia].

作者信息

Mi Rui-Hua, Chen Lin, Zhou Ya-Lan, Li Dong-Bei, Liu Sha, Wang Xiao-Jiao, Liu Jia, Wang Min-Fang, Ma Xiao-Miao, Li Zhi-Chun, Zhao Hong-Mian, Xu Yu-Lin, Chen Shu-Xia, Yang Hai-Ping, Guo Zhi-Qiang, Luan Chun-Lai, Guo Shu-Li, Song Qing-Lin, Wei Xu-Dong

机构信息

Cancer Hospital Affiliated to Zhengzhou University/Henan Cancer Hospital, Zhengzhou 450008, Henan Province, China.

Pingdingshan First People's Hospital, Pingdingshan 467000, Henan Province, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2021 Feb;29(1):26-31. doi: 10.19746/j.cnki.issn.1009-2137.2021.01.004.

Abstract

OBJECTIVE

To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML).

METHODS

Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls.

RESULTS

The ratio of CD4/CD8 T cells, the percentage of NK cells, the expression of perforin and Granzyme B of NK cells in the peripheral blood of patients with hematological malignancies were lower than those of healthy controls. The level of VEGF, IL-6 and TNF-α in the peripheral plasma were higher than those of the healthy control group, and the difference was statistically significant. The level of IFN-γ was lower, and the difference was not statistically significant. The ratio of CD4/CD8 T cells, the percentage of NK cells, the expression of Granzyme B and Perforin of NK cells in peripheral blood were higher after the therapy of thalidomide combined with rhIFNα-1b for 3 months as compared with those before treatment of ITI, the level of the IFN-γ in peripheral plasma was higher while that of VEGF was lower, the difference was statistically significant; after treatment, the ratio of CD3 CD4 and CD3 CD8 lymphocytes and the level of TNF-α in peripheral blood were higher those that before treatment, IL-6 was lower, while the difference was not statistically significant.

CONCLUSION

The ITI regimen can raise the ratio of CD4/CD8 T cells and the percentage of natural killer cells, also, can enhance the generation of perforin and granzyme B and the concentration of IFN-γ as well as inhibit the generation of VEGF, suggesting that these activities may enhance the antitumour capacity of patients with AML.

摘要

目的

探讨干扰素α-1b、白细胞介素-2和沙利度胺(ITI)方案对急性髓系白血病(AML)患者的协同免疫调节机制。

方法

2016年3月至2019年5月,郑州大学附属肿瘤医院及其他11个医疗单位收治的68例未经治疗的初发、复发、难治或维持治疗的AML患者接受ITI方案治疗。每位患者在给予ITI前及治疗3个月后采集外周血标本,置于EDTA-K3抗凝真空管中;采用流式细胞术分析外周血淋巴细胞亚群以及穿孔素和颗粒酶B的表达;采用细胞计数珠阵列检测血浆中VEGF、IFN-γ、TNF-α和IL-6的水平。选取医院体检中心的35名健康受试者作为正常对照。

结果

血液系统恶性肿瘤患者外周血中CD4/CD8 T细胞比值、NK细胞百分比、NK细胞穿孔素和颗粒酶B的表达均低于健康对照。外周血浆中VEGF、IL-6和TNF-α水平高于健康对照组,差异有统计学意义。IFN-γ水平较低,差异无统计学意义。与ITI治疗前相比,沙利度胺联合重组人干扰素α-1b治疗3个月后,外周血中CD4/CD8 T细胞比值、NK细胞百分比、NK细胞颗粒酶B和穿孔素的表达升高,外周血浆中IFN-γ水平升高而VEGF水平降低,差异有统计学意义;治疗后,外周血中CD3 CD4和CD3 CD8淋巴细胞比值及TNF-α水平高于治疗前,IL-6较低,差异无统计学意义。

结论

ITI方案可提高CD4/CD8 T细胞比值和自然杀伤细胞百分比,还可增强穿孔素和颗粒酶B的生成以及IFN-γ的浓度,并抑制VEGF的生成,提示这些作用可能增强AML患者的抗肿瘤能力。

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