EGFR-TKI down-regulates PD-L1 in EGFR mutant NSCLC through inhibiting NF-κB
EGFR-TKI down-regulates PD-L1 in EGFR mutant NSCLC through inhibiting NF-κB
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DOI：
10.1016/j.bbrc.2015.05.030
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发表时间：
2015-07-17
影响因子：
3.1
通讯作者：
Zhu, Bo
中科院分区：
文献类型：
--
作者：
Lin, Kailong;Cheng, Jianan;Zhu, Bo
非小细胞肺癌（NSCLC）是威胁人类健康的严重疾病。表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）的靶向治疗在NSCLC患者的治疗中取得了有效的疗效。然而，EGFR-TKIs对肿瘤免疫微环境的影响尚不清楚。在这项研究中，我们发现具有 EGFR 突变的 NSCLC 比具有野生型 EGFR 的 NSCLC 表达更高的程序性细胞死亡配体 1 (PD-L1)。 EGFR 激活还与 PD-L1 的高表达相关。 EGFR-TKI 吉非替尼可以通过抑制 NF-κ B 在体外和体内的 EGFR 突变 NSCLC 中降低 PD-L1 表达。这些发现阐明了EGFR-TKI新的抗肿瘤机制，为EGFR突变NSCLC患者的靶向治疗和免疫治疗联合策略提供了可能性。 (C) 2015 Elsevier Inc. 保留所有权利。
Non-small-cell lung cancer (NSCLC) is a severe disease threatening human health. Targeted therapy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has obtained potent efficacy in the treatment of NSCLC patients. However, the effects of EGFR-TKIs on tumor immune microenvironment are unclear. In this study, we show that NSCLCs with EGFR mutation express higher programmed cell death ligand 1 (PD-L1) than NSCLCs with wild type EGFR. The EGFR activation is also associated with high expression of PD-L1. The EGFR-TKI gefitinib can reduce PD-L1 expression, via inhibiting NF-kappa B, in EGFR mutant NSCLC in vitro and in vivo. These findings elucidate a novel anti-tumor mechanism of EGFR-TKI and provide the possibility of combined strategy of targeted therapy and immunotherapy for EGFR mutant NSCLC patients. (C) 2015 Elsevier Inc. All rights reserved.