High levels of PD-L1 on platelets of NSCLC patients contributes to the pharmacological activity of Atezolizumab
Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved..
Several studies have associated platelets (PLTs) to NSCLC prognosis. To understand the role of PLTs in immunotherapy-treated patients, we used blood samples of NSCLC patients at different TNM stage. We found that PLTs count and the expression of PD-L1 (pPD-L1) were significantly higher in NSCLC patients at Stage IV than Stage I-III and healthy subjects. The presence of high pPD-L1 was associated to upregulated genes for the extracellular matrix organization and tumor immunosuppression. When patients' survival was correlated to the levels of pPD-L1, longer survival rate was observed, but not when progression disease occurred. The in vitro stimulation of pPD-L1 with Atezolizumab induced CXCL4 release, accompanied by higher levels of TGFβ at the time of drug resistance when the levels of CD16, CD32 and CD64 significantly increased. Leiden-clustering method defined the phenotype of PLTs which showed that the ezrin-radixin-moesin (ERM) family proteins, underlying the PD-L1 signalosome, were involved in high pPD-L1 and higher survival rate. These data imply that Stage IV NSCLC patients characterized by high pPD-L1 are associated with longer progression-free survival rate because the blockade of pPD-L1 by Atezolizumab avoids the exacerbation of a T cell-mediated immune-suppressive environment. pPD-L1 could be an easy-to-use clinical approach to predict ICI responsiveness.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:168 |
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| Enthalten in: |
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie - 168(2023) vom: 15. Dez., Seite 115709 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Colarusso, Chiara [VerfasserIn] |
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| Links: |
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| Themen: |
52CMI0WC3Y |
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| Anmerkungen: |
Date Completed 15.11.2023 Date Revised 29.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.biopha.2023.115709 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363496955 |
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| 520 | |a Several studies have associated platelets (PLTs) to NSCLC prognosis. To understand the role of PLTs in immunotherapy-treated patients, we used blood samples of NSCLC patients at different TNM stage. We found that PLTs count and the expression of PD-L1 (pPD-L1) were significantly higher in NSCLC patients at Stage IV than Stage I-III and healthy subjects. The presence of high pPD-L1 was associated to upregulated genes for the extracellular matrix organization and tumor immunosuppression. When patients' survival was correlated to the levels of pPD-L1, longer survival rate was observed, but not when progression disease occurred. The in vitro stimulation of pPD-L1 with Atezolizumab induced CXCL4 release, accompanied by higher levels of TGFβ at the time of drug resistance when the levels of CD16, CD32 and CD64 significantly increased. Leiden-clustering method defined the phenotype of PLTs which showed that the ezrin-radixin-moesin (ERM) family proteins, underlying the PD-L1 signalosome, were involved in high pPD-L1 and higher survival rate. These data imply that Stage IV NSCLC patients characterized by high pPD-L1 are associated with longer progression-free survival rate because the blockade of pPD-L1 by Atezolizumab avoids the exacerbation of a T cell-mediated immune-suppressive environment. pPD-L1 could be an easy-to-use clinical approach to predict ICI responsiveness | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Non-small cell lung cancer (NSCLC) | |
| 650 | 4 | |a Platelets (PLTs) | |
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| 700 | 1 | |a Somma, Pasquale |e verfasserin |4 aut | |
| 700 | 1 | |a Sommella, Eduardo Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Caponigro, Vichy |e verfasserin |4 aut | |
| 700 | 1 | |a Panico, Luigi |e verfasserin |4 aut | |
| 700 | 1 | |a Salviati, Emanuela |e verfasserin |4 aut | |
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| 700 | 1 | |a Sorrentino, Rosalinda |e verfasserin |4 aut | |
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