The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity
Open accessAbstract
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 synthase kinase 3β (GSK3β) interacts with PD-L1 and induces phosphorylation-dependent proteasome degradation of PD-L1 by β-TrCP. In-depth analysis of PD-L1 N192, N200 and N219 glycosylation suggests that glycosylation antagonizes GSK3β binding. In this regard, only non-glycosylated PD-L1 forms a complex with GSK3β and β-TrCP. We also demonstrate that epidermal growth factor (EGF) stabilizes PD-L1 via GSK3β inactivation in basal-like breast cancer. Inhibition of EGF signalling by gefitinib destabilizes PD-L1, enhances antitumour T-cell immunity and therapeutic efficacy of PD-1 blockade in syngeneic mouse models. Together, our results link ubiquitination and glycosylation pathways to the stringent regulation of PD-L1, which could lead to potential therapeutic strategies to enhance cancer immune therapy efficacy.
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Cites
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
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Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity
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Self-citationIκB Kinase Promotes Tumorigenesis through Inhibition of Forkhead FOXO3a
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Jiang, X., Wang, J., Deng, X., Xiong, F., Ge, J., Xiang, B., Wu, X., Ma, J., Zhou, M., Li, X., et al. (2019) · Molecular Cancer · doi:10.1186/s12943-018-0928-4 · Cited by 1,457
Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory
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Cyclin D–CDK4 kinase destabilizes PD-L1 via cullin 3–SPOP to control cancer immune surveillance
Zhang, J., Bu, X., Wang, H., Zhu, Y., Geng, Y., Nihira, N. T., Tan, Y., Ci, Y., Wu, F., Dai, X., et al. (2018) · Nature · doi:10.1038/nature25015 · Cited by 1,013
PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression
Jiao, S., Xia, W., Yamaguchi, H., Wei, Y., Chen, M.-K., Hsu, J.-M., Hsu, J. L., Yu, W.-H., Du, Y., Lee, H.-H., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-3215 · Cited by 981
Self-citationCMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity
Burr, M. L., Sparbier, C. E., Chan, Y.-C., Williamson, J. C., Woods, K., Beavis, P. A., Lam, E. Y. N., Henderson, M. A., Bell, C. C., Stolzenburg, S., et al. (2017) · Nature · doi:10.1038/nature23643 · Cited by 946
Metadata
- Authors
- Li, C.-W., Lim, S.-O., Xia, W., Lee, H.-H., Chan, L.-C., Kuo, C.-W., Khoo, K.-H., Chang, S.-S., Cha, J.-H., Kim, T., Hsu, J. L., Wu, Y., Hsu, J.-M., Yamaguchi, H., Ding, Q., Wang, Y., Yao, J., Lee, C.-C., Wu, H.-J., Sahin, A. A., Allison, J. P., Yu, D., Hortobagyi, G. N., & Hung, M.-C.
- Venue
- Nature Communications
- Published
- 2016-08-30
- Volume
- 7
- Issue
- 1
- Pages
- 12632-12632
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2516619560
- Cited by
- 1,091
- References
- 9
- FWCI
- 24.26
- Type
- journal article
- Language
- en
- Open access
- gold
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- Li, C.-W., Lim, S.-O., Xia, W., Lee, H.-H., Chan, L.-C., Kuo, C.-W., Khoo, K.-H., Chang, S.-S., Cha, J.-H., Kim, T., Hsu, J. L., Wu, Y., Hsu, J.-M., Yamaguchi, H., Ding, Q., Wang, Y., Yao, J., Lee, C.-C., Wu, H.-J., . . . Hung, M.-C. (2016). Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity. Nature Communications. https://doi.org/10.1038/ncomms12632
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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.
