明胶海绵微粒TACE治疗Barcelona临床肝癌分期B期肝细胞癌对外周血中髓系来源抑制性细胞的影响
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摘要
目的探讨应用明胶海绵微粒TACE(GSMs-TACE)治疗Barcelona临床肿瘤(BCLC)分期B期肝细胞癌(HCC)对患者外周血中髓系来源抑制性细胞(MDSCs)的影响。方法对5例临床确诊为BCLC B期的HCC患者(HCC组)行GSMs-TACE治疗。采用流式细胞仪分别检测患者术前、术后10天及术后30天外周血中MDSCs频率(即MDSCs细胞团占HLA-DR~-细胞群的比例)。另收集7名健康志愿者(正常对照组),于HCC组术前同期进行MDSCs频率检测。比较HCC患者术前及术后不同时间MDSCs频率的差异及HCC组术前与正常对照组同期MDSCs频率的差异。结果 HCC组GSMs-TACE术前外周血中MDSCs频率为(30.26±12.12)%,术后10天降至(10.22±3.79%),术后30天降至(7.33±3.38)%,总体差异有统计学意义(P<0.001);两两比较显示术后30天(P<0.001)及术后10天(P=0.011)均明显低于术前。HCC组术前MDSCs频率明显高于正常对照组同期水平[(30.26±12.12)%vs (3.41±1.89)%,t=5.876,P<0.001)。结论 BCLC B期HCC患者经GSMs-TACE治疗后外周血中MDSCs频率显著降低;GSMs-TACE对患者的机体免疫功能具有正向调节作用。
Objective To investigate the influence of gelatin sponge microparticles-TACE(GSMs-TACE) on myeloid-derived suppressor cells(MDSCs) in peripheral blood of patients with Barcelona clinic liver cancer(BCLC) classification stage B hepatocellular carcinoma(HCC). Methods Five patients with clinically diagnosed BCLC B-stage HCC(HCC group) underwent GSMs-TACE. Flow cytometry was used to detect the frequency of MDSCs(the proportion of MDSCs clusters to HLA-DR~-cell) in the peripheral blood of patients before GSMs-TACE and 10 days as well as 30 days after operation, respectively. Seven healthy volunteers(normal control group) were enrolled. The MDSCs frequency of normal control group was detected simultaneously with HCC group before GSMs-TACE. Statistical analysis was performed to compare the differences of the frequency of MDSCs in HCC patients before and after GSMs-TACE. And the frequency of MDSCs of HCC group was compared with that of normal control group. Results The frequency of MDSCs in peripheral blood of patients with HCC before GSMs-TACE was(30.26±12.12)%, which decreased to(10.22±3.79)% after 10 days and decreased to(7.33±3.38)% after 30 days(P<0.001). Pairwise comparison showed that the frequency of MDSCs at 30 days(P<0.001) and 10 days(P=0.011) after GSMs-TACE was lower than that before operation,respectively. The frequency of preoperative MDSCs of HCC group was statistically higher than that of normal control group([30.26±12.12]% vs [3.41±1.89]%, t=5.876, P<0.001). Conclusion The frequency of MDSCs in peripheral blood of patients with BCLC B-stage HCC significantly reduced after GSMs-TACE treatment. GSMs-TACE treatment has positive regulation effect on the immune function of patients.
Objective To investigate the influence of gelatin sponge microparticles-TACE(GSMs-TACE) on myeloid-derived suppressor cells(MDSCs) in peripheral blood of patients with Barcelona clinic liver cancer(BCLC) classification stage B hepatocellular carcinoma(HCC). Methods Five patients with clinically diagnosed BCLC B-stage HCC(HCC group) underwent GSMs-TACE. Flow cytometry was used to detect the frequency of MDSCs(the proportion of MDSCs clusters to HLA-DR~-cell) in the peripheral blood of patients before GSMs-TACE and 10 days as well as 30 days after operation, respectively. Seven healthy volunteers(normal control group) were enrolled. The MDSCs frequency of normal control group was detected simultaneously with HCC group before GSMs-TACE. Statistical analysis was performed to compare the differences of the frequency of MDSCs in HCC patients before and after GSMs-TACE. And the frequency of MDSCs of HCC group was compared with that of normal control group. Results The frequency of MDSCs in peripheral blood of patients with HCC before GSMs-TACE was(30.26±12.12)%, which decreased to(10.22±3.79)% after 10 days and decreased to(7.33±3.38)% after 30 days(P<0.001). Pairwise comparison showed that the frequency of MDSCs at 30 days(P<0.001) and 10 days(P=0.011) after GSMs-TACE was lower than that before operation,respectively. The frequency of preoperative MDSCs of HCC group was statistically higher than that of normal control group([30.26±12.12]% vs [3.41±1.89]%, t=5.876, P<0.001). Conclusion The frequency of MDSCs in peripheral blood of patients with BCLC B-stage HCC significantly reduced after GSMs-TACE treatment. GSMs-TACE treatment has positive regulation effect on the immune function of patients.
引文
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[11] Wang Y,Luo F,Yang J,et al.New chimeric antigen receptor design for solid tumors.Front Immunol,2017,8:1934.
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[2] Llovet JM,Bruix J.Novel advancements in the management of hepatocellular carcinoma in 2008.J Hepatol,2008,48(Suppl 1):S20-S37.
[3] Chang CJ,Yang YH,Chiu CJ,et al.Targeting tumor-infiltrating Ly6G\\r,+\\r,myeloid cells improves sorafenib efficacy in mouse orthotopic hepatocellular carcinoma.Int J Cancer,2018,142(9):1878-1889.
[4] Mizukoshi E,Yamashita T,Arai K,et al.Myeloid-derived suppressor cells correlate with patient outcomes in hepatic arterial infusion chemotherapy for hepatocellular carcinoma.Cancer Immunol Immunother,2016,65(6):715-725.
[5] Wang N,Lv YZ,Xu AH,et al.Application of lobaplatin in trans-catheter arterial chemoembolization for primary hepatic carcinoma.Asian Pac J Cancer Prev,2014,15(2):647-650.
[6] Lencioni R.New data supporting modified RECIST (mRECIST) forhepatocellular carcinoma.Clin Cancer Res,2013,19(6):1312-1314.
[7] Gabrilovich DI,Ostrand-Rosenberg S,Bronte V.Coordinated regulation of myeloid cells by tumours.Nat Rev Immunol,2012,12(4):253-268.
[8] Heimbach J,Kulik LM,Finn R,et al.AASLD guidelines for the treatment of hepatocellular carcinoma.Hepatology,2017,67(1):358-380.
[9] Kamran AU,Liu Y,Li FE,et al.Transcatheter arterial chemoembolization with gelatin sponge microparticles treated for BCLC stage B hepatocellular carcinoma:A single center retrospective study.Medicine (Baltimore),2015,94(52):e2154.
[10] 刘松,孟冉冉,张跃伟.经肝动脉化疗栓塞与树突状细胞治疗肝癌对机体免疫功能的影响.介入放射学杂志,2014,23(2):181-184.
[11] Wang Y,Luo F,Yang J,et al.New chimeric antigen receptor design for solid tumors.Front Immunol,2017,8:1934.
[12] Nan J,Xing YF,Hu B,et al.Endoplasmic reticulum stress induced Lox-1+CD15+ polymorphonuclear myeloid-derived suppressor cells in hepatocellular carcinoma.Immunology,2018,154(1):144-155.
[13] Hoechst B,Ormandy LA,Ballmaier M,et al.A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+)CD25(+)Foxp3(+) T cells.Gastroenterology,2008,135(1):234-243.
[14] Weber R,Fleming V,Hu X,et al.Myeloid-derived suppressor cells hinder the anti-cancer activity of immune checkpoint inhibitors.Front Immunol,2018,9:1310.