Low-dose photodynamic therapy promotes a cytotoxic immunological response in a murine model of pleural mesothelioma.
Eur J Cardiothorac Surg
; 58(4): 783-791, 2020 10 01.
Article
em En
| MEDLINE
| ID: mdl-32372095
ABSTRACT
OBJECTIVES:
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.METHODS:
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.RESULTS:
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.CONCLUSIONS:
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fotoquimioterapia
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Neoplasias Pleurais
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Neoplasias Pulmonares
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Mesotelioma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article