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Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients

The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant...

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Autores principales: Martino, EC, Misso, G, Pastina, P, Costantini, S, Vanni, F, Gandolfo, C, Botta, C, Capone, F, Lombardi, A, Pirtoli, L, Tassone, P, Ulivieri, C, Tagliaferri, P, Cusi, MG, Caraglia, M, Correale, P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045963/
https://www.ncbi.nlm.nih.gov/pubmed/27752361
http://dx.doi.org/10.1038/cddiscovery.2016.25
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author Martino, EC
Misso, G
Pastina, P
Costantini, S
Vanni, F
Gandolfo, C
Botta, C
Capone, F
Lombardi, A
Pirtoli, L
Tassone, P
Ulivieri, C
Tagliaferri, P
Cusi, MG
Caraglia, M
Correale, P
author_facet Martino, EC
Misso, G
Pastina, P
Costantini, S
Vanni, F
Gandolfo, C
Botta, C
Capone, F
Lombardi, A
Pirtoli, L
Tassone, P
Ulivieri, C
Tagliaferri, P
Cusi, MG
Caraglia, M
Correale, P
author_sort Martino, EC
collection PubMed
description The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects. For this reason, we performed an immunological monitoring in 59 out of 120 stage IIIb-IV NSCLC patients enrolled in the BEVA2007 phase II trial, who received fractioned cisplatin (30 mg/sqm days 1-3q21) and oral etoposide (50 mg, days 1-15q21) (mPE doublet) ±bevacizumab. In this group of patients, 12 received the mPE doublet alone and 47 the doublet in combination with bevacizumab (5 mg/kg on the day 3q21; mPEBev regimen). Blood cell counts, serum analysis, multiplex cytokine assay and immunocytofluorimetric analysis, performed on baseline and post-treatment on blood samples from these patients, revealed that bevacizumab addition to the doublet decreased levels of pro-angiogenic (VEGF, Angiostatin-1 and Follistatin) and inflammatory cytokines (interferon (IFN)γ, IL4 and IL17), improved in vivo and in vitro cytotoxic T-lymphocytes (CTL) response and promoted dendritic cell activation. These results suggest that the mPEBev regimen improve the micro-environmental conditions for an efficient antigen-specific CTL response, making it a feasible candidate regimen to be assessed in combination with immune-checkpoint inhibitors in NSCLC patients.
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spelling pubmed-50459632016-10-17 Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients Martino, EC Misso, G Pastina, P Costantini, S Vanni, F Gandolfo, C Botta, C Capone, F Lombardi, A Pirtoli, L Tassone, P Ulivieri, C Tagliaferri, P Cusi, MG Caraglia, M Correale, P Cell Death Discov Article The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects. For this reason, we performed an immunological monitoring in 59 out of 120 stage IIIb-IV NSCLC patients enrolled in the BEVA2007 phase II trial, who received fractioned cisplatin (30 mg/sqm days 1-3q21) and oral etoposide (50 mg, days 1-15q21) (mPE doublet) ±bevacizumab. In this group of patients, 12 received the mPE doublet alone and 47 the doublet in combination with bevacizumab (5 mg/kg on the day 3q21; mPEBev regimen). Blood cell counts, serum analysis, multiplex cytokine assay and immunocytofluorimetric analysis, performed on baseline and post-treatment on blood samples from these patients, revealed that bevacizumab addition to the doublet decreased levels of pro-angiogenic (VEGF, Angiostatin-1 and Follistatin) and inflammatory cytokines (interferon (IFN)γ, IL4 and IL17), improved in vivo and in vitro cytotoxic T-lymphocytes (CTL) response and promoted dendritic cell activation. These results suggest that the mPEBev regimen improve the micro-environmental conditions for an efficient antigen-specific CTL response, making it a feasible candidate regimen to be assessed in combination with immune-checkpoint inhibitors in NSCLC patients. Nature Publishing Group 2016-10-03 /pmc/articles/PMC5045963/ /pubmed/27752361 http://dx.doi.org/10.1038/cddiscovery.2016.25 Text en Copyright © 2016 Cell Death Differentiation Association http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Martino, EC
Misso, G
Pastina, P
Costantini, S
Vanni, F
Gandolfo, C
Botta, C
Capone, F
Lombardi, A
Pirtoli, L
Tassone, P
Ulivieri, C
Tagliaferri, P
Cusi, MG
Caraglia, M
Correale, P
Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients
title Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients
title_full Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients
title_fullStr Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients
title_full_unstemmed Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients
title_short Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients
title_sort immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045963/
https://www.ncbi.nlm.nih.gov/pubmed/27752361
http://dx.doi.org/10.1038/cddiscovery.2016.25
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