Titre
Low-dose photodynamic therapy promotes a cytotoxic immunological response in a murine model of pleural mesothelioma.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Cavin, S.
Auteure/Auteur
Gkasti, A.
Auteure/Auteur
Faget, J.
Auteure/Auteur
Hao, Y.
Auteure/Auteur
Letovanec, I.
Auteure/Auteur
Reichenbach, M.
Auteure/Auteur
Gonzalez, M.
Auteure/Auteur
Krueger, T.
Auteure/Auteur
Dyson, P.J.
Auteure/Auteur
Meylan, E.
Auteure/Auteur
Perentes, J.Y.
Auteure/Auteur
Liens vers les unités
ISSN
1873-734X
Statut éditorial
Publié
Date de publication
2020-10-01
Volume
58
Numéro
4
Première page
783
Dernière page/numéro d’article
791
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Malignant pleural mesothelioma (MPM) is a deadly disease with limited treatment options. Approaches to enhance patient immunity against MPM have been tested but shown variable results. Previously, we have demonstrated interesting vascular modulating properties of low-dose photodynamic therapy (L-PDT) on MPM. Here, we hypothesized that L-PDT vascular modulation could favour immune cell extravasation in MPM and improve tumour control in combination with immune checkpoint inhibitors.
First, we assessed the impact of L-PDT on vascular endothelial E-selectin expression, a key molecule for immune cell extravasation, in vitro and in a syngeneic murine model of MPM. Second, we characterized the tumour immune cell infiltrate by 15-colour flow cytometry analysis 2 and 7 days after L-PDT treatment of the murine MPM model. Third, we determined how L-PDT combined with immune checkpoint inhibitor anti-CTLA4 affected tumour growth in a murine MPM model.
L-PDT significantly enhanced E-selectin expression by endothelial cells in vitro and in vivo. This correlated with increased CD8+ T cells and activated antigen-presenting cells (CD11b+ dendritic cells and macrophages) infiltration in MPM. Also, compared to anti-CTLA4 that only affects tumour growth, the combination of L-PDT with anti-CTLA4 caused complete MPM regression in 37.5% of animals.
L-PDT enhances E-selectin expression in the MPM endothelium, which favours immune infiltration of tumours. The combination of L-PDT with immune checkpoint inhibitor anti-CTLA4 allows best tumour control and regression.
First, we assessed the impact of L-PDT on vascular endothelial E-selectin expression, a key molecule for immune cell extravasation, in vitro and in a syngeneic murine model of MPM. Second, we characterized the tumour immune cell infiltrate by 15-colour flow cytometry analysis 2 and 7 days after L-PDT treatment of the murine MPM model. Third, we determined how L-PDT combined with immune checkpoint inhibitor anti-CTLA4 affected tumour growth in a murine MPM model.
L-PDT significantly enhanced E-selectin expression by endothelial cells in vitro and in vivo. This correlated with increased CD8+ T cells and activated antigen-presenting cells (CD11b+ dendritic cells and macrophages) infiltration in MPM. Also, compared to anti-CTLA4 that only affects tumour growth, the combination of L-PDT with anti-CTLA4 caused complete MPM regression in 37.5% of animals.
L-PDT enhances E-selectin expression in the MPM endothelium, which favours immune infiltration of tumours. The combination of L-PDT with immune checkpoint inhibitor anti-CTLA4 allows best tumour control and regression.
PID Serval
serval:BIB_3B7D8E7DB62D
PMID
Date de création
2020-05-08T13:31:09.188Z
Date de création dans IRIS
2025-05-20T17:24:53Z
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Cavin EJCTS.pdf
Version du manuscrit
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Format
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Nom
Cavin EJCTS supplemental.pdf
Version du manuscrit
postprint
Taille
1.65 MB
Format
Adobe PDF
PID Serval
serval:BIB_3B7D8E7DB62D.S001
Somme de contrôle
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