MDSC在儿童急性B淋巴细胞白血病发病中的作用

发布时间：2018-05-25 02:20

本文选题：急性B淋巴细胞白血病 + 髓源性抑制细胞　；参考：《遵义医学院》2016年硕士论文

【摘要】：目的:髓源性抑制细胞(myeloid-derived suppressor cells,MDSC)是近年发现的一种具有免疫抑制功能的细胞,参与肿瘤的免疫逃逸,促进肿瘤生长。目前国内外对于MDSC的研究主要集中在荷瘤小鼠和成人实体瘤,白血病方面仅有个别报道。本课题旨在通过研究急性B淋巴细胞白血病(acute B lymphoblastic leukemia,B-ALL)患儿外周血中MDSC数目、亚群比例、主要功能物质变化,以及对NK细胞的影响,探讨MDSC在儿童B-ALL发病中的作用,有助于进一步阐明儿童ALL的发病机制,并为制定相关的免疫靶向治疗提供理论依据。方法:收集初诊治疗前和完全缓解后B-ALL患儿及健康儿童外周血,采用流式细胞术(FCM)检测各组外周血中MDSC(CD11b+CD33+)的数量变化;两种不同亚群:单核细胞样MDSC(CD14+CD11b+CD33+)和粒细胞样MDSC(CD15+CD11b+CD33+)的比例及其变化情况;以及MDSC主要功能物质精氨酸酶1(Arg-1)和活性氧物质(ROS)的表达情况;同时检测各组外周血中NK细胞活化所必需的表面受体NKG2D的表达水平。结果:1.治疗前B-ALL患儿外周血中MDSC数量比例(2.41%±0.45%)明显高于完全缓解组(1.56%±0.44%)及正常组(0.68%±0.16%)(F=92.094,P0.01);且MDSC数量比例与不同危险度分层呈正相关(r s=0.680,P0.01),即MDSC数量比例随危险度分层升高而增加,不同危险度分层间MDSC的数量比例差异也具有统计学意义(F=23.360,P0.01);治疗前B-ALL外周血MDSC亚群以粒细胞样MDSC(G-MDSC)为主,完全缓解后B-ALL患儿与正常对照外周血中MDSC亚群组成无明显差别,且均以单核细胞样MDSC(M-MDSC)为主。2.外周血MDSC中Arg-1和ROS的在治疗前B-ALL患儿表达最高(41.00%±9.34%;3004.26±611.05),完全缓解后次之(24.13%±5.49%;2031.75±294.01),正常对照组表达最低(10.72%±4.37%;811.33±195.12)(F=95.285,P0.01;F=124.089,P0.01);Arg-1的表达随ALL危险度分层升高有上升趋势,但差异无统计意义(F=1.373,P=0.265);不同危险度分层中ROS表达具有统计学差异(F=6.363,P0.01),其中高危组表达明显高于中危组和标危组,中危和标危组的表达差异无统计学意义。3.B-ALL患儿外周血NK中NKG2D的比例在治疗前(21.35%±5.94%)和完全缓解后(14.28%±4.59%)均明显低于正常对照(35.51%±5.25%)(F=78.589,P0.01),且与MDSC数量比例呈负相关(r=㧟0.558,P0.01),随MDSC数量增加而降低。结论:1.MDSC在B-ALL患儿外周血中数量增加,且危险度分层越高增加越明显,其治疗前亚群以G-MDSC为主,在治疗后MDSC的数量降低,亚群组成趋于正常,以M-MDSC为主。2.MDSC两种主要功能物质Arg-1和ROS在治疗前B-ALL患儿中表达最高,完全缓解后明显下降但仍高于正常儿童。3.B-ALL患儿外周血NK细胞中NKG2D的比例明显低于正常且与MDSC数量比例呈负相关。4.B-ALL患儿中MDSC数量、亚群以及主要功能物质均发生明显变化,同时伴有NK细胞功能下降,本研究结果提示MDSC可能通过抑制机体免疫功能,增加肿瘤的免疫逃逸从而参与儿童B-ALL的发病。
[Abstract]:Objective: Myeloid-derived suppressor cells (MDSCs) is an immunosuppressive cell found in recent years, which participates in the immune escape of tumor and promotes tumor growth. At present, the research on MDSC is mainly focused on tumor-bearing mice and adult solid tumors, leukemia is only reported. The purpose of this study was to investigate the role of MDSC in the pathogenesis of B-ALL in children with acute B lymphocyte leukemia (ACL) by studying the number of MDSC, the proportion of subsets, the changes of main functional substances and the effect on NK cells in the peripheral blood of children with acute B lymphoblastic leukemia. It is helpful to elucidate the pathogenesis of ALL in children and provide theoretical basis for the development of immunoreactive therapy. Methods: the peripheral blood of children with B-ALL and healthy children were collected before and after initial treatment and complete remission. Flow cytometry (FCM) was used to detect the quantity of MDSC(CD11b CD33 in peripheral blood of each group. Two different subgroups: monocyte-like MDSC(CD14 CD11b CD33) and granulocyte-like MDSC(CD15 CD11b CD33 (MDSC(CD15 CD11b CD33), and the expression of argininase 1 (Arg-1) and reactive oxygen species (Ros) in MDSC; At the same time, the expression of NKG2D, which is necessary for NK cell activation, was detected. The result is 1: 1. Before treatment, the proportion of MDSC in peripheral blood of children with B-ALL was 2.41% 卤0.45%) significantly higher than that of complete remission group (1.56% 卤0.44%) and normal group (0.68% 卤0.160.094%, P 0.01), and there was a positive correlation between MDSC quantity and different risk stratification, that is, the proportion of MDSC increased with the increase of risk stratification. Before treatment, the MDSC subsets in peripheral blood of B-ALL were mainly granulocyte-like MDSC-G-MDSC.There was no significant difference in MDSC subgroup between children with B-ALL and normal controls after complete remission. The monocyte like MDSCM-MDSCM-MDSC2 was the main one. The expression of Arg-1 and ROS in peripheral blood MDSC was the highest in children with B-ALL before treatment (41.00% 卤9.34), followed by 24.13% 卤5.493.75 卤294.01% after complete remission. The lowest expression of Arg-1 and ROS in normal control group was 10.72% 卤4.37%. The expression of Arg-1 was increased with the increase of ALL risk stratification. However, there was no statistical significance in the expression of ROS in different risk stratification. The expression of ROS in high risk group was significantly higher than that in middle risk group and standard risk group. There was no significant difference in the expression of NK NKG2D between the middle risk group and the standard risk group. 3. The percentage of NK NKG2D in peripheral blood of children with moderate risk and standard risk group was 21.35% 卤5.94% before treatment and 14.28% 卤4.59% after complete remission. It was significantly lower than that of normal control group (35.51% 卤5.2558% 卤78.589P 0.01a), and negatively correlated with the ratio of MDSC. Conclusion: 1. The number of MDSC in peripheral blood of children with B-ALL increased, and the higher the risk stratification, the more obvious. The subgroup of MDSC was mainly G-MDSC before treatment. After treatment, the number of MDSC decreased and the subgroup became normal. 2. The expression of Arg-1 and ROS, two main functional substances of MDSC, were the highest in children with B-ALL before treatment. After complete remission, the percentage of NKG2D in peripheral blood NK cells in children with complete remission was significantly lower than that in normal children. 3. The percentage of NKG2D in peripheral blood NK cells was significantly lower than that in normal children and negatively correlated with the proportion of MDSC. The results suggest that MDSC may play a role in the pathogenesis of B-ALL in children by inhibiting the immune function of the body and increasing the immune escape of the tumor.
【学位授予单位】：遵义医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R733.71

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