PD-L1/PD-1 blockage enhanced the cytotoxicity of natural killer cell on the non-small cell lung cancer (NSCLC) by granzyme B secretion
© 2023. The Author(s)..
OBJECTIVE: To explore the role of PD-L1/PD-1 blockage in the cytotoxicity of natural killer cell in NSCLC.
METHODS: Two NSCLC cell lines, Calu-1 and H460, were tested for susceptibility to the cytolytic activity of freshly isolated healthy donor NK cells by a non-radioactive cellular cytotoxicity assay kit. Western blot analysis, FACS, ELISA and antibody blockage experiments were conducted to determine the mechanisms. NK cells isolated from NSCLC patients were also collected for functional assays.
RESULTS: Calu-1 and H460 cells were lysed by NK cells in a dose-dependent manner. H460 cells showed less susceptibility to NK cell-mediated lysis than Calu-1 cells at all ratios. The expression of PD-L1 on H460 cells was higher than that on Calu-1 cells, as determined by FACS and western blot analysis. The specific lysis of H460 cells by NK cells was enhanced when the PD-L1/PD-1 interaction was blocked by anti-PD-L1 antibody. This finding was also demonstrated in NK cells isolated from NSCLC patients.
CONCLUSIONS: The present study revealed that PD-L1/PD-1 blockage enhanced the cytotoxicity of natural killer cells in NSCLC via granzyme B secretion. This study will greatly facilitate the precise treatment of lung cancer through determination of PD-L1 expression in tumors.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico - 25(2023), 8 vom: 01. Aug., Seite 2373-2383 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Qiao, Duan-Rui [VerfasserIn] |
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| Links: |
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| Themen: |
EC 3.4.21.- |
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| Anmerkungen: |
Date Completed 28.06.2023 Date Revised 01.07.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s12094-023-03120-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM353629189 |
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| 245 | 1 | 0 | |a PD-L1/PD-1 blockage enhanced the cytotoxicity of natural killer cell on the non-small cell lung cancer (NSCLC) by granzyme B secretion |
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| 500 | |a Date Completed 28.06.2023 | ||
| 500 | |a Date Revised 01.07.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a OBJECTIVE: To explore the role of PD-L1/PD-1 blockage in the cytotoxicity of natural killer cell in NSCLC | ||
| 520 | |a METHODS: Two NSCLC cell lines, Calu-1 and H460, were tested for susceptibility to the cytolytic activity of freshly isolated healthy donor NK cells by a non-radioactive cellular cytotoxicity assay kit. Western blot analysis, FACS, ELISA and antibody blockage experiments were conducted to determine the mechanisms. NK cells isolated from NSCLC patients were also collected for functional assays | ||
| 520 | |a RESULTS: Calu-1 and H460 cells were lysed by NK cells in a dose-dependent manner. H460 cells showed less susceptibility to NK cell-mediated lysis than Calu-1 cells at all ratios. The expression of PD-L1 on H460 cells was higher than that on Calu-1 cells, as determined by FACS and western blot analysis. The specific lysis of H460 cells by NK cells was enhanced when the PD-L1/PD-1 interaction was blocked by anti-PD-L1 antibody. This finding was also demonstrated in NK cells isolated from NSCLC patients | ||
| 520 | |a CONCLUSIONS: The present study revealed that PD-L1/PD-1 blockage enhanced the cytotoxicity of natural killer cells in NSCLC via granzyme B secretion. This study will greatly facilitate the precise treatment of lung cancer through determination of PD-L1 expression in tumors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Granzyme B | |
| 650 | 4 | |a NK cells | |
| 650 | 4 | |a Non-small cell lung cancer | |
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| 700 | 1 | |a Yan, Wei-Qun |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hai-Jun |e verfasserin |4 aut | |
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