朗格汉斯细胞源外泌体负载多肽抗原/佐剂的抗肿瘤效果研究
Journal: Basic Medical Theory Research DOI: 10.12238/bmtr.v7i5.16507
Abstract
朗格汉斯细胞(Langerhans Cells, LCs)作为强效的抗原提呈细胞,其来源的外泌体(Exosomes, Exos)作为细胞间通讯的载体,在肿瘤免疫中发挥重要作用。本研究旨在探讨以HPV16 E6多肽片段(E6)作为宫颈癌肿瘤免疫抗原,以CpG寡聚脱氧核苷酸链(Cytosine-Phosphate-Guanine Oligodeoxynucleotide,CpG ODN)作为免疫佐剂,联合刺激朗格汉斯细胞产生的外泌体(LC-Exos)作为治疗性疫苗,评估其诱导的细胞毒性T淋巴细胞(Cytotoxic T Lymphocyte,CTL)对宫颈癌细胞的杀伤活性及潜在的抗肿瘤效果。通过分离培养人外周血单核细胞,诱导分化为朗格汉斯细胞。然后分别利用PBS(对照组)、HPV16 E6多肽(E组)、CpG ODN(P组)、E6多肽联合CpG ODN(E+P组)刺激LCs。提取上述各组LCs分泌的外泌体。将各组外泌体与自体T细胞共培养,诱导产生特异性CTL。采用MTT法检测各组CTL在不同效靶比下对HPV16阳性宫颈癌细胞株(SiHa)的杀伤活性。以人肝癌细胞株(HepG2)作为非特异性对照靶细胞。计算杀伤率,并进行统计学分析。E+P组CTL对宫颈癌细胞的杀伤率最高,显著高于E组、P组、对照组(P<0.01)。E组和P组的杀伤率也显著高于对照组(P<0.05)。随着效靶比的降低,各组CTL的杀伤活性均有所下降,但E+P组在各效靶比下均显示出最优的杀伤效果。HPV16 E6多肽联合CpG ODN刺激的朗格汉斯细胞源外泌体能够有效诱导产生特异性CTL,并对HPV16阳性的宫颈癌细胞表现出较强的、特异性的杀伤效应。
Keywords
宫颈癌；朗格汉斯细胞；外泌体；抗原提呈；免疫治疗
Funding
2021年盐城市医学科技发展计划项目(普通项目)“朗格汉斯细胞外泌体对宫颈癌细胞免疫作用研究”(YK2021098)。
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