LPS alters the immuno-phenotype of glioma and glioma stem-like cells and induces in vivo antitumor immunity via TLR4.
LPS alters the immuno-phenotype of glioma and glioma stem-like cells and induces in vivo antitumor immunity via TLR4.
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LPS 改变神经胶质瘤和神经胶质瘤干细胞样细胞的免疫表型，并通过 TLR4 诱导体内抗肿瘤免疫
DOI：
10.1186/s13046-017-0552-y
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发表时间：
2017-06-22
期刊：
影响因子：
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通讯作者：
Wu A
中科院分区：
文献类型：
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作者：
Han S;Wang C;Qin X;Xia J;Wu A
本研究研究了脂多糖（LPS）在体外对胶质瘤和胶质瘤干细胞样细胞（GSCs）的影响，以及在体内诱导抗肿瘤免疫的能力，以及TLR4在这些过程中的作用。方法采用RT-PCR和免疫组织化学方法检测34例胶质母细胞瘤临床标本中TLR4的表达。采用real - time-PCR、western blot和ELISA分析，评价LPS刺激对RG2和U87 GSCs免疫相关分子表达的影响。对照或lps预处理的RG2 GSCs被植入野生型或裸Fisher 344大鼠的脑内或皮下。采用组织病理学检查评估肿瘤进展和免疫浸润，Kaplan-Meier分析比较动物模型的生存时间。结果stlr4在胶质母细胞瘤临床标本中高表达。体外LPS刺激6小时显著改变RG2和U87 GSCs中免疫相关分子的表达。然而，长时间的LPS刺激会减弱这种效果。脑内接种lps预处理RG2 GSCs的大鼠存活时间明显长于对照组RG2 GSCs。在体内，lps预处理的RG2 GSCs表达更高水平的MHC分子、CXCL10和TNF-α，募集更多的CD8+淋巴细胞。然而，瘤内LPS治疗并不同样有益。此外，LPS刺激的体内和体外效应似乎主要依赖于tlr4。结论在荷瘤宿主免疫功能完好的情况下，lps预处理可促进体内肿瘤GSCs的识别和清除。此外，我们的数据表明细菌感染与胶质瘤预后之间存在复杂的关系。
BackgroundThis study examined the ability of lipopolysaccharide (LPS) to affect glioma and glioma stem-like cells (GSCs) in vitro and to induce antitumor immunity in vivo and the role of TLR4 in these processes.MethodsUsing RT-PCR and immunohistochemistry, we examined the expression of TLR4 in 34 glioblastoma clinical samples. Using real time-PCR, western blot and ELISA analyses, the effect of LPS stimulation on the expression of immune related molecules was evaluated in RG2 and U87 GSCs. Control or LPS-pretreated RG2 GSCs were intracranially or subcutaneously implanted into wild-type or nude Fisher 344 rats. Histopathological examinations were used to assess tumor progression and immune infiltration and Kaplan-Meier analyses to compare survival times of the animal models.ResultsTLR4 was highly expressed in glioblastoma clinical samples. In vitro LPS stimulation for 6 h significantly altered expression of immune related molecules in RG2 and U87 GSCs. However, prolonged LPS stimulation diminished this effect. Rats inoculated intracranially with LPS-pretreated RG2 GSCs survived significantly longer than rats inoculated with control RG2 GSCs. In vivo, LPS-pretreated RG2 GSCs expressed higher levels of MHC molecules, CXCL10 and TNF-α and recruited more CD8+lymphocytes. However, intratumoral LPS treatment was not equally beneficial. Furthermore, the in vitro and in vivo effects of LPS stimulation appeared to be largely TLR4-dependent.ConclusionLPS pretreatment promotes the recognition and eradication of tumor GSCs in vivo when the immune function of the tumor-bearing host is intact. In addition, our data indicate a complex relationship between bacterial infection and glioma prognosis.