Bevacizumab specifically decreases elevated levels of circulating KIT+CD11b+ cells and IL-10 in metastatic breast cancer patients.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_D03DFDC56AE2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Bevacizumab specifically decreases elevated levels of circulating KIT+CD11b+ cells and IL-10 in metastatic breast cancer patients.
Périodique
Oncotarget
Auteur(s)
Cattin S., Fellay B., Pradervand S., Trojan A., Ruhstaller T., Rüegg C., Fürstenberger G.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Statut éditorial
Publié
Date de publication
08/03/2016
Peer-reviewed
Oui
Volume
7
Numéro
10
Pages
11137-11150
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Whether bevacizumab exerts its anti-tumor properties through systemic effects beyond local inhibition of angiogenesis and how these effects can be monitored in patients, remain largely elusive. To address these questions, we investigated bone marrow-derived cells and cytokines in the peripheral blood of metastatic breast cancer patients undergoing therapy with bevacizumab.
Circulating endothelial cells (CEC), circulating endothelial progenitor (CEP) and circulating CD11b+ cells in metastatic breast cancer patients before and during therapy with paclitaxel alone (n = 11) or in combination with bevacizumab (n = 10) were characterized using flow cytometry, real time PCR and RNASeq. Circulating factors were measured by ELISA. Aged-matched healthy donors were used as baseline controls (n = 12).
Breast cancer patients had elevated frequencies of CEC, CEP, TIE2+CD11b+ and KIT+CD11b+ cell subsets. CEC decreased during therapy, irrespective of bevacizumab, while TIE2+CD11b+ remained unchanged. KIT+CD11b+ cells decreased in response to paclitaxel with bevacizumab, but not paclitaxel alone. Cancer patients expressed higher mRNA levels of the M2 polarization markers CD163, ARG1 and IL-10 in CD11b+ cells and increased levels of the M2 cytokines IL-10 and CCL20 in plasma. M1 activation markers and cytokines were low or equally expressed in cancer patients compared to healthy donors. Chemotherapy with paclitaxel and bevacizumab, but not with paclitaxel alone, significantly decreased IL-10 mRNA in CD11b+ cells and IL-10 protein in plasma.
This pilot study provides evidence of systemic immunomodulatory effects of bevacizumab and identified circulating KIT+CD11b+ cells and IL-10 as candidate biomarkers of bevacizumab activity in metastatic breast cancer patients.

Mots-clé
Adult, Aged, Angiogenesis Inhibitors/therapeutic use, Bevacizumab/therapeutic use, Bone Marrow Cells/drug effects, Bone Marrow Cells/pathology, Breast Neoplasms/blood, Breast Neoplasms/drug therapy, Breast Neoplasms/pathology, CD11b Antigen/metabolism, Endothelial Cells/drug effects, Endothelial Cells/pathology, Female, Humans, Interleukin-10/metabolism, Middle Aged, Monocytes/pathology, Paclitaxel/therapeutic use, Pilot Projects, Proto-Oncogene Proteins c-kit/metabolism, Stem Cells/drug effects, Stem Cells/pathology, IL-10, KIT, angiogenesis, breast cancer, monocytes
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/02/2016 16:11
Dernière modification de la notice
20/08/2019 15:50
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