Triptolide reduces PD-L1 through the EGFR and IFN-γ/IRF1 dual signaling pathways
Copyright © 2023 Elsevier B.V. All rights reserved..
As the principal ligand of programmed death 1 (PD-1), PD-L1 can induce the exhaustion of effector T cells and the escape of cancer cells through interacting with PD-1 in many solid malignancies. Therefore, targeting the PD-1/PD-L1 axis has become an attractive strategy in cancer immunotherapy. However, at present, no small-molecule agents targeting PD1/PD-L1 pathways have been successfully used in clinical applications. Here, we first found that the natural product Triptolide could significantly reduce the PD-L1 expression on the surface of NSCLC cells. This down-regulation is related to the activity of EGFR signaling pathway. Moreover, the reduction of PD-L1 caused by Triptolide could be substantially rescued by IFN-γ. Furthermore, our findings suggest that Triptolide significantly inhibits the activity of the IFN-γ-JAK-STAT-IRF1 signaling axis, as evidenced by the noticeable reduction in both basal and phosphorylated levels of STAT3. Thus, in NSCLC cells, Triptolide reduces PD-L1 expression both through the EGFR and IFN-γ/JAK1/JAK2/STAT1/STAT3/IRF1 signaling pathways. The results provide new insights into the application of Triptolide in the immune checkpoints treatment of NSCLCs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:118 |
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| Enthalten in: |
International immunopharmacology - 118(2023) vom: 01. Mai, Seite 109993 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xie, Yongli [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.04.2023 Date Revised 25.04.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2023.109993 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a As the principal ligand of programmed death 1 (PD-1), PD-L1 can induce the exhaustion of effector T cells and the escape of cancer cells through interacting with PD-1 in many solid malignancies. Therefore, targeting the PD-1/PD-L1 axis has become an attractive strategy in cancer immunotherapy. However, at present, no small-molecule agents targeting PD1/PD-L1 pathways have been successfully used in clinical applications. Here, we first found that the natural product Triptolide could significantly reduce the PD-L1 expression on the surface of NSCLC cells. This down-regulation is related to the activity of EGFR signaling pathway. Moreover, the reduction of PD-L1 caused by Triptolide could be substantially rescued by IFN-γ. Furthermore, our findings suggest that Triptolide significantly inhibits the activity of the IFN-γ-JAK-STAT-IRF1 signaling axis, as evidenced by the noticeable reduction in both basal and phosphorylated levels of STAT3. Thus, in NSCLC cells, Triptolide reduces PD-L1 expression both through the EGFR and IFN-γ/JAK1/JAK2/STAT1/STAT3/IRF1 signaling pathways. The results provide new insights into the application of Triptolide in the immune checkpoints treatment of NSCLCs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a EGFR | |
| 650 | 4 | |a NSCLC | |
| 650 | 4 | |a PD-L1 | |
| 650 | 4 | |a Protein downregulation | |
| 650 | 4 | |a Triptolide | |
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| 700 | 1 | |a Ding, Jiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Jieke |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jiantao |e verfasserin |4 aut | |
| 700 | 1 | |a Cen, Shan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jinming |e verfasserin |4 aut | |
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