In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 4122-4122
Abstract:
Programmed death ligand-1 (PD-L1) is an important immune checkpoint molecule that allows cancer cells to evade immune surveillance. Further, the PD-L1 level is relatively higher in tumor tissues compared to normal tissues. Thus, the PD-L1/PD-1 axis has served as primary target for cancer immunotherapy. However, the regulatory mechanisms of PD-L1 level are not fully understood. Here, we demonstrated that the ER-associated degradation (ERAD) mechanism of PD-L1 through cross-talking between phosphorylation and glycosylation. We discover that AMP-activated protein kinase (AMPK) activated by metformin directly binds with PD-L1 in the ER lumen and phosphorylates Ser 195 of PD-L1. The Ser 195 phosphorylation induces abnormal mannose-rich glycan structures of PD-L1 through excessive ER trimming process. PD-L1 with abnormal glycan structures is occupied by ER quality check components in the ER and finally degraded through ERAD pathway. We provide new insights to understand cancer immune checkpoints by identifying a new regulatory mechanism of PD-L1 and these findings can be used to improve the efficacy of previous cancer immunotherapy for the PD-L / PD-1 axis. Citation Format: Jong-Ho Cha, Wen-Hao Yang, Weiya Xia, Yongkun Wei, Li-Chuan Chan, Chia-Wei Li, Heng-Huan Lee, Mien-Chie Hung. The regulatory mechanism of PD-L1 level through ER-associated degradation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4122.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2019-4122
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2019
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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