Low-dose photodynamic therapy promotes a cytotoxic immunological response in a murine model of pleural mesothelioma.

Details

Serval ID
serval:BIB_3B7D8E7DB62D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Low-dose photodynamic therapy promotes a cytotoxic immunological response in a murine model of pleural mesothelioma.
Journal
European journal of cardio-thoracic surgery
Author(s)
Cavin S., Gkasti A., Faget J., Hao Y., Letovanec I., Reichenbach M., Gonzalez M., Krueger T., Dyson P.J., Meylan E., Perentes J.Y.
ISSN
1873-734X (Electronic)
ISSN-L
1010-7940
Publication state
Published
Issued date
01/10/2020
Peer-reviewed
Oui
Volume
58
Number
4
Pages
783-791
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
Immunotherapy, Malignant pleural mesothelioma, Photodynamic therapy
Pubmed
Web of science
Create date
08/05/2020 15:31
Last modification date
17/04/2021 6:34
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