The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion
Open accessAbstract
Enriched PD-L1 expression in cancer stem-like cells (CSCs) contributes to CSC immune evasion. However, the mechanisms underlying PD-L1 enrichment in CSCs remain unclear. Here, we demonstrate that epithelial–mesenchymal transition (EMT) enriches PD-L1 in CSCs by the EMT/β-catenin/STT3/PD-L1 signaling axis, in which EMT transcriptionally induces N-glycosyltransferase STT3 through β-catenin, and subsequent STT3-dependent PD-L1 N-glycosylation stabilizes and upregulates PD-L1. The axis is also utilized by the general cancer cell population, but it has much more profound effect on CSCs as EMT induces more STT3 in CSCs than in non-CSCs. We further identify a non-canonical mesenchymal–epithelial transition (MET) activity of etoposide, which suppresses the EMT/β-catenin/STT3/PD-L1 axis through TOP2B degradation-dependent nuclear β-catenin reduction, leading to PD-L1 downregulation of CSCs and non-CSCs and sensitization of cancer cells to anti-Tim-3 therapy. Together, our results link MET to PD-L1 stabilization through glycosylation regulation and reveal it as a potential strategy to enhance cancer immunotherapy efficacy.
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Cites
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Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
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Cited by
Immune checkpoint signaling and cancer immunotherapy
He, X., & Xu, C. (2020) · Cell Research · doi:10.1038/s41422-020-0343-4 · Cited by 1,371
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-citationRegulatory mechanisms of PD-1/PD-L1 in cancers
Lin, X., Kang, K., Chen, P., Zeng, Z., Li, G., Xiong, W., Yi, M., & Xiang, B. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02023-w · Cited by 784
Regulation of PD-L1 expression in the tumor microenvironment
Yi, M., Niu, M., Xu, L., Luo, S., & Wu, K. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-01027-5 · Cited by 681
Cancer stem cell–immune cell crosstalk in tumour progression
Bayik, D., & Lathia, J. D. (2021) · Nature Reviews Cancer · doi:10.1038/s41568-021-00366-w · Cited by 561
Metadata
- Authors
- Hsu, J.-M., Xia, W., Hsu, Y.-H., Chan, L.-C., Yu, W.-H., Cha, J.-H., Chen, C.-T., Liao, H.-W., Kuo, C.-W., Khoo, K.-H., Hsu, J. L., Li, C.-W., Lim, S.-O., Chang, S.-S., Chen, Y.-C., Ren, G.-X., & Hung, M.-C.
- Venue
- Nature Communications
- Published
- 2018-05-15
- Volume
- 9
- Issue
- 1
- Pages
- 1908-1908
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2804930677
- Cited by
- 434
- References
- 58
- FWCI
- 13.14
- Type
- journal article
- Language
- en
- Open access
- gold
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- Hsu, J.-M., Xia, W., Hsu, Y.-H., Chan, L.-C., Yu, W.-H., Cha, J.-H., Chen, C.-T., Liao, H.-W., Kuo, C.-W., Khoo, K.-H., Hsu, J. L., Li, C.-W., Lim, S.-O., Chang, S.-S., Chen, Y.-C., Ren, G.-X., & Hung, M.-C. (2018). STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion. Nature Communications. https://doi.org/10.1038/s41467-018-04313-6
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