Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity

• Published in: Nature communications Vol. 7; no. 1; pp. 12632 - 11
• Main Authors: Li, Chia-Wei, Lim, Seung-Oe, Xia, Weiya, Lee, Heng-Huan, Chan, Li-Chuan, Kuo, Chu-Wei, Khoo, Kay-Hooi, Chang, Shih-Shin, Cha, Jong-Ho, Kim, Taewan, Hsu, Jennifer L., Wu, Yun, Hsu, Jung-Mao, Yamaguchi, Hirohito, Ding, Qingqing, Wang, Yan, Yao, Jun, Lee, Cheng-Chung, Wu, Hsing-Ju, Sahin, Aysegul A., Allison, James P., Yu, Dihua, Hortobagyi, Gabriel N., Hung, Mien-Chie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.08.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 14/1; 38/70; 631/250/580; 631/67/1059/2325; 631/67/1347; 631/80/458/1524; 64; 64/60; 82/58; Animal models; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; B7-H1 Antigen - immunology; B7-H1 Antigen - metabolism; beta-Transducin Repeat-Containing Proteins - metabolism; Breast - pathology; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Cancer; Cell death; Cell Line, Tumor; Deactivation; Epidermal growth factor; Epidermal Growth Factor - metabolism; Female; Gefitinib; Glycogen; Glycogen synthase kinase 3; Glycogen Synthase Kinase 3 beta - metabolism; Glycosylation; Growth factors; Humanities and Social Sciences; Humans; Immunity; Immunologic Surveillance - immunology; Immunosuppression; Inactivation; Kinases; Ligands; Lymphocyte Activation - immunology; Lymphocytes T; Mice; Mice, Inbred BALB C; Mortality; multidisciplinary; PD-1 protein; PD-L1 protein; Phosphorylation; Programmed Cell Death 1 Receptor - metabolism; Proteasomes; Protein Stability - drug effects; Proteins; Quinazolines - pharmacology; Quinazolines - therapeutic use; Science; Science (multidisciplinary); Signal transduction; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tumor Escape - immunology; Tumors; Ubiquitination; Xenograft Model Antitumor Assays

Extracellular interaction between programmed death ligand-1 (PD-L1) and programmed cell death protein-1 (PD-1) leads to tumour-associated immune escape. Here we show that the immunosuppression activity of PD-L1 is stringently modulated by ubiquitination and N -glycosylation. We show that glycogen sy...