TLR3 triggering regulates PD-L1 (CD274) expression in human neuroblastoma cells
TLR3 triggering regulates PD-L1 (CD274) expression in human neuroblastoma cells
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DOI：
10.1016/j.canlet.2015.02.027
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发表时间：
2015-05-28
期刊：
影响因子：
9.7
通讯作者：
Meyer-Wentrup, Friederike
中科院分区：
文献类型：
--
作者：
Boes, Marianne;Meyer-Wentrup, Friederike
神经母细胞瘤是儿童中最常见的颅外实体瘤，占儿童癌症死亡率的12%。神经母细胞瘤特异性t细胞已在患者体内检测到，但通常不能攻击和根除肿瘤。因此，肿瘤免疫逃避可能在神经母细胞瘤的致病性中起重要作用。最近对成人癌症患者的研究表明，靶向t细胞检查点分子PD-1/PD-L1（或CD279/CD274）可能增强对实体肿瘤的免疫反应性。此外，感染可能与自发性神经母细胞瘤消退有关。因此，在我们目前的研究中，我们研究了靶向PD-L1的抗体和触发选择性病原体受体toll样受体（TLRs）是否增强了神经母细胞瘤细胞的免疫原性。我们发现情况就是这样。TLR3触发诱导MHC类和PD-L1对神经母细胞瘤细胞的强烈上调。同时降低tgf - β水平，诱导IL-8分泌。使用PD-L1阻断和使用病毒类似物poly（I:C）触发TLR3联合治疗神经母细胞瘤细胞还诱导CD4（+）和CD8(+) t细胞活化。因此，我们建议将PD-L1阻断与合成TLR配体联合治疗作为一种新的免疫治疗人类神经母细胞瘤的途径。2015爱思唯尔爱尔兰有限公司版权所有，
Neuroblastoma is the most common extracranial solid tumor in children, causing 12% of all pediatric cancer mortality. Neuroblastoma specific T-cells have been detected in patients, but usually fail to attack and eradicate the tumors. Tumor immune evasion may thus play an important role in neuroblastoma pathogenicity. Recent research in adult cancer patients shows that targeting T-cell check-point molecules PD-1/PD-L1 (or CD279/CD274) may bolster immune reactivity against solid tumors. Also, infections can be associated with spontaneous neuroblastoma regression. In our current study, we therefore investigated if antibody targeting of PD-L1 and triggering of selective pathogen-receptor Toll-like receptors (TLRs) potentiates immunogenicity of neuroblastoma cells. We find this to be the case. TLR3 triggering induced strong upregulation of both MHC class land PD-L1 on neuroblastoma cells. At the same time TGF-beta levels decreased and IL-8 secretion was induced. The combined neuroblastoma cell treatment using PD-L1 blockade and TLR3 triggering using virus analog poly(I:C) moreover induced CD4(+) and CD8(+) T-cell activation. Thus, we propose combined treatment using PD-L1 blockade with synthetic TLR ligands as an avenue toward new immunotherapy against human neuroblastoma. (C) 2015 Elsevier Ireland Ltd. All rights reserved,