ENO1 promotes antitumor immunity by destabilizing PD-L1 in NSCLC
ENO1 promotes antitumor immunity by destabilizing PD-L1 in NSCLC
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ENO1 通过破坏 NSCLC 中 PD-L1 的稳定性来促进抗肿瘤免疫
DOI：
10.1038/s41423-021-00710-y
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发表时间：
2021
影响因子：
24.1
通讯作者：
D. Ge
中科院分区：
文献类型：
--
作者：
Chunyi Zhang;Kunpeng Zhang;Jie Gu;D. Ge
PD-L1通过结合T细胞上的配体PD-1，在抑制T细胞活性和驱动肿瘤细胞逃避免疫监视中起重要作用。1几种细胞内和细胞外因子，如干扰素- γ（IFN- γ）、MYC、转化生长因子β和miR-200，可能通过转录和转录后机制调节PD-L1表达。2 - 5在这里，我们发现了一种新的蛋白质ENO 1参与PD-L1的调节。在肺癌细胞中，ENO 1可通过促进PD-L1泛素化和随后的蛋白酶体降解而使PD-L1不稳定并降低其表达。肺癌组织芯片也显示，ENO 1的表达与PD-L1呈负相关。此外，在同基因小鼠模型中，ENO 1的过表达使肿瘤细胞对特异性T细胞杀伤敏感，并增加了T细胞介导的抗肿瘤免疫力。在这项研究中，我们首先使用免疫沉淀结合质谱（IP-MS）来寻找PD-L1表达的新调节剂。SDS-聚丙烯酰胺凝胶电泳的考马斯亮蓝染色显示V5结合免疫沉淀物中有一条约50 kDa的条带（补充图S1），MS在条带中艾德由来自ENO 1的10个连续氨基酸组成的序列（补充图S2）。共IP实验证明，在H1299和SPC-A-1细胞中，ENO 1与PD-L1相互作用，PD-L1和ENO 1表达增加（图1A和补充图S3）。然后，我们检测了ENO 1蛋白的积累是否有助于调节
PD-L1 plays an important role in inhibiting T-cell activity and driving tumor cell escape from immune surveillance by binding its ligand, PD-1, on T cells. 1 Several intracellular and extracellular factors, such as interferon- γ (IFN- γ ), MYC, transforming growth factor β , and miR-200, may modulate PD-L1 expression by transcriptional and posttranscriptional mechanisms. 2 – 5 Here we discovered that ENO1, a novel protein, is involved in the regulation of PD-L1. ENO1 could destabilize PD-L1 and decrease its expression by promoting PD-L1 ubiquitination and subsequent proteasomal degradation in lung cancer cells. A lung cancer tissue microarray also showed that the expression of ENO1 was negatively correlated with PD-L1. Furthermore, overexpression of ENO1 sensitized tumor cells to speci fi c T-cell killing and increased T-cell-mediated antitumor immunity in syngeneic mouse models. In this study, we fi rst used immunoprecipitation coupled with mass spectrometry (IP-MS) to seek new regulators of PD-L1 expression. Coomassie blue staining of SDS-polyacrylamide gel electrophoresis revealed an ~50 kDa band in V5-bound immuno- precipitates (Supplementary Fig. S1) and MS identi fi ed a sequence consisting of ten consecutive amino acids from ENO1 in the band (Supplementary Fig. S2). A co-IP experiment proved that ENO1 interacted with PD-L1 in H1299 and SPC-A-1 cells with increased PD- L1 and ENO1 expression (Fig. 1A and Supplementary Fig. S3). Then, we detected whether ENO1 protein accumulation contributes to modulating
影响因子：
50.3
作者：
Lim SO;Li CW;Xia W;Cha JH;Chan LC;Wu Y;Chang SS;Lin WC;Hsu JM;Hsu YH;Kim T;Chang WC;Hsu JL;Yamaguchi H;Ding Q;Wang Y;Yang Y;Chen CH;Sahin AA;Yu D;Hortobagyi GN;Hung MC
通讯作者：
Hung MC