Abstract：
UNASSIGNED: Myeloid-derived suppressor cells (MDSCs) are evolving as a prominent determinant in cancer occurrence and development and are functionally found to suppress T cells in cancer. Not much research is done regarding its involvement in viral infections. This research was designed to investigate the role of MDSCs in hepatitis B virus (HBV) infection and how targeting these cells with our novel all-trans retinoic acid encapsulated liposomal formulation could improve immunotherapy in C57BL/6 mice.
UNASSIGNED: Ten micrograms (10 μg) of plasmid adeno-associated virus (pAAV/HBV 1.2, genotype A) was injected hydrodynamically via the tail vein of C57BL/6 mice. An all-trans retinoic acid encapsulated liposomal formulation (L-ATRA) with sustained release properties was used in combination with tenofovir disoproxil fumarate (TDF), a nucleotide analog reverse transcriptase inhibitor (nRTI) to treat the HBV infection. The L-ATRA formulation was given at a dose of 5 mg/kg intravenously (IV) twice a week. The TDF was given orally at 30 mg/kg daily.
UNASSIGNED: Our results revealed that L-ATRA suppresses MDSCs in HBV infected mice and enhanced T-cell proliferation in vitro. In vivo studies showed higher and improved immunotherapeutic effect in mice that received L-ATRA and TDF concurrently in comparison with the groups that received monotherapy. Lower HBV DNA copies, lower concentrations of HBsAg and HBeAg, lower levels of ALT and AST and less liver damage were seen in the mice that received the combination therapy of L-ATRA + TDF.
UNASSIGNED: In effect, targeting MDSCs with the combination of L-ATRA and TDF effectively reduced mMDSC and improved immunotherapy in the HBV infected mice. Targeting MDSCs could provide a breakthrough in the fight against hepatitis B virus infection.
UNASSIGNED: Ten micrograms (10 μg) of plasmid adeno-associated virus (pAAV/HBV 1.2, genotype A) was injected hydrodynamically via the tail vein of C57BL/6 mice. An all-trans retinoic acid encapsulated liposomal formulation (L-ATRA) with sustained release properties was used in combination with tenofovir disoproxil fumarate (TDF), a nucleotide analog reverse transcriptase inhibitor (nRTI) to treat the HBV infection. The L-ATRA formulation was given at a dose of 5 mg/kg intravenously (IV) twice a week. The TDF was given orally at 30 mg/kg daily.
UNASSIGNED: Our results revealed that L-ATRA suppresses MDSCs in HBV infected mice and enhanced T-cell proliferation in vitro. In vivo studies showed higher and improved immunotherapeutic effect in mice that received L-ATRA and TDF concurrently in comparison with the groups that received monotherapy. Lower HBV DNA copies, lower concentrations of HBsAg and HBeAg, lower levels of ALT and AST and less liver damage were seen in the mice that received the combination therapy of L-ATRA + TDF.
UNASSIGNED: In effect, targeting MDSCs with the combination of L-ATRA and TDF effectively reduced mMDSC and improved immunotherapy in the HBV infected mice. Targeting MDSCs could provide a breakthrough in the fight against hepatitis B virus infection.
摘要：
■髓系来源的抑制细胞(MDSC)作为癌症发生和发展中的突出决定因素进化,并且在功能上发现抑制癌症中的T细胞。关于其参与病毒感染的研究并不多。这项研究旨在研究MDSCs在乙型肝炎病毒（HBV）感染中的作用，以及如何用我们的新型全反式维甲酸包封的脂质体制剂靶向这些细胞可以改善C57BL/6小鼠的免疫治疗。
■通过C57BL/6小鼠的尾静脉以流体动力学方式注射10微克（10μg）的质粒腺相关病毒（pAAV/HBV1.2，基因型A）。具有缓释特性的全反式维甲酸包封的脂质体制剂（L-ATRA）与富马酸替诺福韦酯（TDF）联合使用，核苷酸类似物逆转录酶抑制剂（nRTI）治疗HBV感染。L-ATRA制剂以5mg/kg的剂量静脉内(IV)给予,每周两次。TDF以每天30mg/kg口服给药。
■我们的结果表明，L-ATRA抑制HBV感染小鼠的MDSCs，并在体外增强T细胞增殖。体内研究显示，与接受单一疗法的组相比，同时接受L-ATRA和TDF的小鼠具有更高和改善的免疫治疗作用。较低的HBVDNA拷贝，较低浓度的HBsAg和HBeAg，在接受L-ATRA+TDF联合治疗的小鼠中观察到较低水平的ALT和AST以及较少的肝损伤。
■实际上，靶向MDSCs与L-ATRA和TDF的组合有效降低mMDSC和改善在HBV感染小鼠的免疫治疗。靶向MDSCs可以在对抗乙型肝炎病毒感染方面提供突破。
■通过C57BL/6小鼠的尾静脉以流体动力学方式注射10微克（10μg）的质粒腺相关病毒（pAAV/HBV1.2，基因型A）。具有缓释特性的全反式维甲酸包封的脂质体制剂（L-ATRA）与富马酸替诺福韦酯（TDF）联合使用，核苷酸类似物逆转录酶抑制剂（nRTI）治疗HBV感染。L-ATRA制剂以5mg/kg的剂量静脉内(IV)给予,每周两次。TDF以每天30mg/kg口服给药。
■我们的结果表明，L-ATRA抑制HBV感染小鼠的MDSCs，并在体外增强T细胞增殖。体内研究显示，与接受单一疗法的组相比，同时接受L-ATRA和TDF的小鼠具有更高和改善的免疫治疗作用。较低的HBVDNA拷贝，较低浓度的HBsAg和HBeAg，在接受L-ATRA+TDF联合治疗的小鼠中观察到较低水平的ALT和AST以及较少的肝损伤。
■实际上，靶向MDSCs与L-ATRA和TDF的组合有效降低mMDSC和改善在HBV感染小鼠的免疫治疗。靶向MDSCs可以在对抗乙型肝炎病毒感染方面提供突破。
