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 accessAbstract
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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Cited by
Mechanisms Controlling PD-L1 Expression in Cancer
Cha, J.-H., Chan, L.-C., Li, C.-W., Hsu, J. L., & Hung, M.-C. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.09.030 · Cited by 1,045
Self-citationRegulation of PD-L1 expression in the tumor microenvironment
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Targeting cytokine and chemokine signaling pathways for cancer therapy
Yi, M., Li, T., Niu, M., Zhang, H., Wu, Y., Wu, K., & Dai, Z. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01868-3 · Cited by 455
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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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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.