| Objective:This study examined the proportion of myeloid-derived suppressor cells(MDSCs),the expression of programmed death-ligand 1(PD-L1)on MDSCs,interleukin-6(IL-6),interleukin-10(IL-10)and tumor necrosis factor alpha(TNF-a)levels and correlation analysis with Epstein-Barr virus(EBV)infection.To explore the role of MDSCs,PD-L1 and EBV infection in the pathogenesis and clinical significance of MM.Methods:We collected 31 cases of newly diagnosed MM patients from department of hematology of the second hospital of lanzhou university from December 2017 to January 2019,and 9 cases of normal controls were enrolled into the present study.Flow cytometry was used to detect the proportion of MDSCs,the expression of PD-L1 on MDSCs in peripheral blood and the levels of IL-6,IL-10 and TNF-a in peripheral blood serum.Fluorescence quantitative PCR was used to detect EBV-DNA in peripheral blood of MM patients.Then we analyzed the correlation between MDSCs,PD-L1 and IL-6,IL-10,TNF-a and EBV infection..Results:1.Compared with the normal control group,the proportion of MDSCs was significantly increased(31.87±4.48%vs 18.95±2.86%,P<0.001),and the proportion of PD-L1~+MDSCs was significantly increased(25.96±7.63%vs 12.21±3.40%,P<0.001)in the MM group;Compared with the normal control group,the proportion of MDSCs was significantly increased(31.90±4.50%vs 18.95±2.86%,P<0.001),and the proportion of PD-L1~+MDSCs was significantly increased(30.20±7.96%vs 12.21±3.40%,P<0.001)in the EBV-DNA positive MM group;Compared with the EBV-DNA negative MM group,the proportion of MDSCs was no significant difference(31.90±4.50%vs 31.85±4.58%,P=0.97),and the proportion of PD-L1~+MDSCs was increased(30.20±7.96%vs 23.62±6.51%,P<0.05)in the EBV-DNA positive MM group.2.The proportion of MDSCs and the expression of PD-L1 in MM were not correlated with the gender,age of onset and type of immunoglobulin,but correlated with the clinical stage of the disease.Compared with the stageⅠ+ⅡMM patients,the proportion of MDSCs and the expression of PD-L1was increased in the stageⅢMM patients(34.52±5.35%vs 30.41±3.21%,30.80±6.30%vs 23.29±7.07%,P<0.05).3.Compared with the normal control group,the levels of IL-6,IL-10 and TNF-a was increased in the MM group(14.97±3.76pg/ml vs 4.50±1.61pg/ml,19.10±3.57pg/ml vs 4.54±2.11pg/ml,35.87±4.84pg/ml vs 7.45±2.51pg/ml,P<0.001);Compared with the normal control group,the levels of IL-6,IL-10 and TNF-a was increased in the EBV-DNA positive MM group(17.32±3.51pg/ml vs 4.50±1.61pg/ml,21.10±3.00pg/ml vs 4.54±2.11pg/ml,35.04±6.45pg/ml vs 7.45±2.51pg/ml,P<0.001);Compared with the EBV-DNA negative MM group,the levels of IL-6,IL-10 was increased(17.32±3.51pg/ml vs 13.68±3.30pg/ml,21.10±3.00pg/ml vs 17.99±3.43pg/ml,P<0.05),and the levels of TNF-a was no significant difference(35.04±6.45pg/ml vs 36.32±3.80pg/ml,P=0.56)in the EBV-DNA positive MM group.4.In peripheral blood of MM patients,the proportion of MDSCs was positively correlated with the levels of cytokines IL-6(r=0.373,P<0.05),the proportion of MDSCs was positively correlated with the levels of cytokines IL-10(r=0.529,P<0.01),the proportion of MDSCs was positively correlated with the levels of cytokines TNF-a(r=0.495,P<0.01).The expression of PD-L1 on MDSCs was positively correlated with the levels of cytokines IL-6(r=0.674,P<0.01),the expression of PD-L1 on MDSCs was positively correlated with the levels of cytokines IL-10(r=0.588,P<0.01),the expression of PD-L1 on MDSCs was positively correlated with the levels of cytokines TNF-a(r=0.426,P<0.05).Conclusion:1.The proportion of MDSCs and the expression of PD-L1 in MM patients are abnormal,and the levels of related cytokines are abnormal,suggesting that MDSCs and PD-L1 may play an important role in the pathogenesis of MM through immunosuppressive mechanisms.2.The expression of PD-L1 was increased in EBV-positive MM patients,and the levels of cytokines IL-6 and IL-10 were increased,suggesting that EBV may participate in MM immune disorder and pathogenesis by up-regulating PD-L1 expression and inducing cytokines. |
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