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The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.

IL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to promote cancer immune evasion

Open access
Chan, Li-Chuan, Li, Chia-Wei, Xia, Weiya, Hsu, Jung-Mao, Lee, Heng-Huan, Cha, Jong-Ho, Wang, Hung-Ling, Yang, Wen-Hao, Yen, Er-Yen, Chang, Wei-Chao, Zha, Zhengyu, Lim, Seung-Oe, Lai, Yun-Ju, Liu, Chunxiao, Liu, Jielin, Dong, Qiongzhu, Yang, Yi, Sun, Linlin, Wei, Yongkun, Nie, Lei, Hsu, Jennifer L., Li, Hui, Ye, Qinghai, Hassan, Manal M., Amin, Hesham M., Kaseb, Ahmed O., Lin, Xin, Wang, Shao-Chun, Hung, Mien-Chie·2019·Journal of Clinical Investigation

Abstract

Glycosylation of immune receptors and ligands, such as T cell receptor and coinhibitory molecules, regulates immune signaling activation and immune surveillance. However, how oncogenic signaling initiates glycosylation of coinhibitory molecules to induce immunosuppression remains unclear. Here we show that IL-6-activated JAK1 phosphorylates programmed death-ligand 1 (PD-L1) Tyr112, which recruits the endoplasmic reticulum-associated N-glycosyltransferase STT3A to catalyze PD-L1 glycosylation and maintain PD-L1 stability. Targeting of IL-6 by IL-6 antibody induced synergistic T cell killing effects when combined with anti-T cell immunoglobulin mucin-3 (anti-Tim-3) therapy in animal models. A positive correlation between IL-6 and PD-L1 expression was also observed in hepatocellular carcinoma patient tumor tissues. These results identify a mechanism regulating PD-L1 glycosylation initiation and suggest the combination of anti-IL-6 and anti-Tim-3 as an effective marker-guided therapeutic strategy.

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Metadata

Authors
Chan, L.-C., Li, C.-W., Xia, W., Hsu, J.-M., Lee, H.-H., Cha, J.-H., Wang, H.-L., Yang, W.-H., Yen, E.-Y., Chang, W.-C., Zha, Z., Lim, S.-O., Lai, Y.-J., Liu, C., Liu, J., Dong, Q., Yang, Y., Sun, L., Wei, Y., Nie, L., Hsu, J. L., Li, H., Ye, Q., Hassan, M. M., Amin, H. M., Kaseb, A. O., Lin, X., Wang, S.-C., & Hung, M.-C.
Venue
Journal of Clinical Investigation
Published
2019-07-15
Volume
129
Issue
8
Pages
3324-3338
ISSN
  • 0021-9738 (ISSN-L)
  • 1558-8238
OpenAlex
W2961185444
Cited by
382
References
52
FWCI
15.69
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: IL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to promote cancer immune evasion. https://app.cochat.ai/papers/10.1172/jci126022
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Chan, L.-C., Li, C.-W., Xia, W., Hsu, J.-M., Lee, H.-H., Cha, J.-H., Wang, H.-L., Yang, W.-H., Yen, E.-Y., Chang, W.-C., Zha, Z., Lim, S.-O., Lai, Y.-J., Liu, C., Liu, J., Dong, Q., Yang, Y., Sun, L., Wei, Y., . . . Hung, M.-C. (2019). IL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to promote cancer immune evasion. Journal of Clinical Investigation. https://doi.org/10.1172/jci126022

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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