Serum amyloid A promotes glycolysis of neutrophils during PD-1 blockade resistance in hepatocellular carcinoma
© 2024. The Author(s)..
The response to programmed death-1 (PD-1) blockade varies in hepatocellular carcinoma (HCC). We utilize a panel of 16 serum factors to show that a circulating level of serum amyloid A (SAA) > 20.0 mg/L has the highest accuracy in predicting anti-PD-1 resistance in HCC. Further experiments show a correlation between peritumoral SAA expression and circulating SAA levels in patients with progressive disease after PD-1 inhibition. In vitro experiments demonstrate that SAA induces neutrophils to express PD-L1 through glycolytic activation via an LDHA/STAT3 pathway and to release oncostatin M, thereby attenuating cytotoxic T cell function. In vivo, genetic or pharmacological inhibition of STAT3 or SAA eliminates neutrophil-mediated immunosuppression and enhances antitumor efficacy of anti-PD-1 treatment. This study indicates that SAA may be a critical inflammatory cytokine implicated in anti-PD-1 resistance in HCC. Targeting SAA-induced PD-L1+ neutrophils through STAT3 or SAA inhibition may present a potential approach for overcoming anti-PD1 resistance.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature communications - 15(2024), 1 vom: 26. Feb., Seite 1754 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
He, Meng [VerfasserIn] |
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| Links: |
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| Themen: |
B7-H1 Antigen |
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| Anmerkungen: |
Date Completed 28.02.2024 Date Revised 29.02.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-024-46118-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368991652 |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a The response to programmed death-1 (PD-1) blockade varies in hepatocellular carcinoma (HCC). We utilize a panel of 16 serum factors to show that a circulating level of serum amyloid A (SAA) > 20.0 mg/L has the highest accuracy in predicting anti-PD-1 resistance in HCC. Further experiments show a correlation between peritumoral SAA expression and circulating SAA levels in patients with progressive disease after PD-1 inhibition. In vitro experiments demonstrate that SAA induces neutrophils to express PD-L1 through glycolytic activation via an LDHA/STAT3 pathway and to release oncostatin M, thereby attenuating cytotoxic T cell function. In vivo, genetic or pharmacological inhibition of STAT3 or SAA eliminates neutrophil-mediated immunosuppression and enhances antitumor efficacy of anti-PD-1 treatment. This study indicates that SAA may be a critical inflammatory cytokine implicated in anti-PD-1 resistance in HCC. Targeting SAA-induced PD-L1+ neutrophils through STAT3 or SAA inhibition may present a potential approach for overcoming anti-PD1 resistance | ||
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| 700 | 1 | |a Liu, Yongxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Song |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Haijing |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Qiao, Shuang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Qifeng |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Huiming |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xun |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Xiongying |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Xiaojun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Lyu, Ning |e verfasserin |4 aut | |
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