Extracellular vesicles derived from lung cancer cells exposed to intermittent hypoxia upregulate programmed death ligand 1 expression in macrophages
© 2021. The Author(s)..
PURPOSE: Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), compromises immune surveillance through the upregulation of programmed cell death-1 ligand (PD-L1). Tumor-released extracellular vesicles (EVs) have been reported to modulate immunosuppressive activities. We investigated whether or not EVs derived from intermittent hypoxic lung cancer cells can alter the expression of PD-L1 in macrophages.
METHODS: The expression of PD-L1+monocytes from 40 patients with newly diagnosed non-small-cell lung cancer (NSCLC) and with (n=21) or without (n=19) OSA were detected. Plasma EVs isolated from NSCLC patients with moderate-severe OSA (n=4) and without OSA (n=4) were co-cultured with macrophages. A549 cells were exposed to normoxia or IH (48 cycles of 5 min of 1% O2 hypoxia, followed by 5 min of normoxia). EVs were isolated from cell supernatant and were co-cultured with macrophages differentiated from THP-1. PD-L1 and hypoxia-inducible factor-1 α (HIF-1α) expressions were measured by flow cytometry, immunofluorescence, and Western blot analysis.
RESULTS: PD-L1+monocytes were elevated in NSCLC patients with OSA and increased with the severity of OSA and nocturnal desaturation. PD-L1+ macrophages were induced by EVs from NSCLC patients with OSA and positively correlated with HIF-1α expressions. EVs from IH-treated A549 can promote PD-L1 and HIF-1α expression in macrophages and the upregulation of PD-L1 expression was reversed by specific HIF-1α inhibitor.
CONCLUSION: IH can enhance the function of EVs derived from lung cancer cells to aggravate immunosuppressive status in macrophages. HIF-1α may play an important role in this process.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Sleep & breathing = Schlaf & Atmung - 26(2022), 2 vom: 12. Juni, Seite 893-906 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Yuanling [VerfasserIn] |
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| Links: |
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| Themen: |
B7-H1 Antigen |
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| Anmerkungen: |
Date Completed 26.05.2022 Date Revised 16.07.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s11325-021-02369-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM328000035 |
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| 100 | 1 | |a Liu, Yuanling |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Extracellular vesicles derived from lung cancer cells exposed to intermittent hypoxia upregulate programmed death ligand 1 expression in macrophages |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 26.05.2022 | ||
| 500 | |a Date Revised 16.07.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. The Author(s). | ||
| 520 | |a PURPOSE: Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), compromises immune surveillance through the upregulation of programmed cell death-1 ligand (PD-L1). Tumor-released extracellular vesicles (EVs) have been reported to modulate immunosuppressive activities. We investigated whether or not EVs derived from intermittent hypoxic lung cancer cells can alter the expression of PD-L1 in macrophages | ||
| 520 | |a METHODS: The expression of PD-L1+monocytes from 40 patients with newly diagnosed non-small-cell lung cancer (NSCLC) and with (n=21) or without (n=19) OSA were detected. Plasma EVs isolated from NSCLC patients with moderate-severe OSA (n=4) and without OSA (n=4) were co-cultured with macrophages. A549 cells were exposed to normoxia or IH (48 cycles of 5 min of 1% O2 hypoxia, followed by 5 min of normoxia). EVs were isolated from cell supernatant and were co-cultured with macrophages differentiated from THP-1. PD-L1 and hypoxia-inducible factor-1 α (HIF-1α) expressions were measured by flow cytometry, immunofluorescence, and Western blot analysis | ||
| 520 | |a RESULTS: PD-L1+monocytes were elevated in NSCLC patients with OSA and increased with the severity of OSA and nocturnal desaturation. PD-L1+ macrophages were induced by EVs from NSCLC patients with OSA and positively correlated with HIF-1α expressions. EVs from IH-treated A549 can promote PD-L1 and HIF-1α expression in macrophages and the upregulation of PD-L1 expression was reversed by specific HIF-1α inhibitor | ||
| 520 | |a CONCLUSION: IH can enhance the function of EVs derived from lung cancer cells to aggravate immunosuppressive status in macrophages. HIF-1α may play an important role in this process | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Extracellular vesicle | |
| 650 | 4 | |a Macrophage | |
| 650 | 4 | |a Non-small-cell lung cancer | |
| 650 | 4 | |a Obstructive sleep apnea | |
| 650 | 4 | |a Programmed cell death-1 ligand | |
| 650 | 7 | |a B7-H1 Antigen |2 NLM | |
| 650 | 7 | |a Hypoxia-Inducible Factor 1, alpha Subunit |2 NLM | |
| 700 | 1 | |a Lu, Minzhen |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jianan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Siqi |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Yiyu |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Shifang |e verfasserin |4 aut | |
| 700 | 1 | |a Ou, Qiong |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Zeru |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Jianlong |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Xinglin |e verfasserin |4 aut | |
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