| Objective: Myeloid-derived suppressor cells(MDSC) is a kind of cells with immune suppression function. MDSC was shown to target tumor immune escape and promote tumor growth. So far, the most investigations on MDSC were involved in tumor-bearing mice and solid tumors, the significance in leukemias is still needed to be evaluated. Our study aims to demonstrate changes of MDSC and its effect on NK cells in peripheral blood of children with B-cell acute lymphocytic leukemia(B-ALL), so as to explore roles of MDSC in pediatric B-ALL. The study on MDSC may contribute to explain the pathogenesis of pediatric B-ALL and may also provide theoretical basis for its immunotherapy.Methods: Peripheral blood was collected from newly diagnosed B-ALL pediatric patients, patients with complete remission and health children. Flow cytomertry(FCM) was used to detect number of MDSC(CD11b+CD33+), proportion of M-MDSC(CD14+CD11b+CD33+) and G-MDSC(CD15+CD11b+CD33+). The expressions of arginase-1(Arg-1), reactive oxygen species(ROS) and NKG2 D were measured as well.Results: 1. The number of MDSC in the B-ALL patients before treatment(2.41%±0.45%) was significantly higher than those after treatment(1.56%±0.44%) and the healthy controls(0.68%±0.16%)(F=92.094, P<0.01).There was a positive correlation between the number of MDSC and the risk stratifications(rs = 0.680, P<0.01) and significant difference among the three risk groups was observed(F=23.360, P<0.01). G-MDSC was the main subtype in the group before the treatment and M-MDSC was the main subtype in the patients with complete remission and the normal controls. 2. The expressions of Arg-1 and ROS were highest in the groups before treatment(41.00%±9.34%; 3004.26±611.05), the second was the groups of complete remission(24.13%±5.49%; 2031.75±294.01) and the healthy controls was the least(10.72%±4.37%; 811.33±195.12)(F=95.285, P<0.01; F=124.089,P<0.01).Expression of Arg-1 increased by the risk stratifications, but no statistical difference among the three risk groups(F=1.373, P=0.265).The expression of ROS in the high-risk(HR) group was higher than those in the intermediate-risk(IR) and standard-risk(SR) groups(F=6.363, P<0.01), no significant difference between the groups of IR and SR.3. The proportions of NKG2 D in the patients before treatment(21.35%±5.94%) and after treatment(14.28%±4.59%) were lower than that in the healthy controls(35.51%±5.25%)(F=78.589, P<0.01). A negative correlation was observed between MDSC proportion and NKG2 D expression(r =﹣0.558,P<0.01).Conclusion: 1. The MDSC increases significantly in the B-ALL patients and is correlated to the risk stratifications. The main subtype is G-MDSC in the groups before treatment. MDSC decreases and the subtypes tend to be normal after the treatment. 2. Arg-1 and ROS are over expressed in the MDSC from the B-ALL patients. 3. The expression of NKG2 Din the B-ALL patients significantly lower than that in the normal controls and is negative correlated to MDSC. 4. There are significant changes in MDSC for proportions, subtypes and functional molecules in the B-ALL patients with decreased function of the NK cells. Our findings suggest MDSC may play an important role in pathogenesis of B-ALL by immune suppression and enhancement of immune escape. |
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