Interplay between oncolytic measles virus, macrophages and cancer cells induces a proinflammatory tumor microenvironment.

Autor:	Chatelain C; Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, Nantes, France.; LabEx IGO, Nantes Université, Nantes, France., Berland L; Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, Nantes, France.; LabEx IGO, Nantes Université, Nantes, France., Grard M; Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, Nantes, France.; LabEx IGO, Nantes Université, Nantes, France., Jouand N; LabEx IGO, Nantes Université, Nantes, France.; Nantes Université, CHU Nantes, CNRS, Inserm, BioCore, US16, SFR Bonamy, Nantes, France., Fresquet J; Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, Nantes, France.; LabEx IGO, Nantes Université, Nantes, France., Nader J; Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, Nantes, France.; LabEx IGO, Nantes Université, Nantes, France., Hirigoyen U; Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, Nantes, France.; LabEx IGO, Nantes Université, Nantes, France., Petithomme T; Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, Nantes, France.; LabEx IGO, Nantes Université, Nantes, France., Combredet C; Vaccines Innovation Laboratory, Institut Pasteur, Université de Paris Cité, Paris, France., Pons-Tostivint E; Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, Nantes, France.; LabEx IGO, Nantes Université, Nantes, France.; Centre Hospitalier Universitaire Nantes, Medical Oncology, Nantes University, Nantes, France., Fradin D; Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, Nantes, France.; LabEx IGO, Nantes Université, Nantes, France., Treps L; Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, Nantes, France.; LabEx IGO, Nantes Université, Nantes, France., Blanquart C; Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, Nantes, France.; LabEx IGO, Nantes Université, Nantes, France., Boisgerault N; Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, Nantes, France.; LabEx IGO, Nantes Université, Nantes, France., Tangy F; Vaccines Innovation Laboratory, Institut Pasteur, Université de Paris Cité, Paris, France.; Oncovita, Paris, France., Fonteneau JF; Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, Nantes, France.; LabEx IGO, Nantes Université, Nantes, France.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2024 Jul 10; Vol. 13 (1), pp. 2377830. Date of Electronic Publication: 2024 Jul 10 (Print Publication: 2024).
DOI:	10.1080/2162402X.2024.2377830
Abstrakt:	Attenuated measles virus (MV) exerts its oncolytic activity in malignant pleural mesothelioma (MPM) cells that lack type-I interferon (IFN-I) production or responsiveness. However, other cells in the tumor microenvironment (TME), such as myeloid cells, possess functional antiviral pathways. In this study, we aimed to characterize the interplay between MV and the myeloid cells in human MPM. We cocultured MPM cell lines with monocytes or macrophages and infected them with MV. We analyzed the transcriptome of each cell type and studied their secretion and phenotypes by high-dimensional flow cytometry. We also measured transgene expression using an MV encoding GFP (MV-GFP). We show that MPM cells drive the differentiation of monocytes into M2-like macrophages. These macrophages inhibit GFP expression in tumor cells harboring a defect in IFN-I production and a functional signaling downstream of the IFN-I receptor, while having minimal effects on GFP expression in tumor cells with defect of responsiveness to IFN-I. Interestingly, inhibition of the IFN-I signaling by ruxolitinib restores GFP expression in tumor cells. Upon MV infection, cocultured macrophages express antiviral pro-inflammatory genes and induce the expression of IFN-stimulated genes in tumor cells. MV also increases the expression of HLA and costimulatory molecules on macrophages and their phagocytic activity. Finally, MV induces the secretion of inflammatory cytokines, especially IFN-I, and PD-L1 expression in tumor cells and macrophages. These results show that macrophages reduce viral proteins expression in some MPM cell lines through their IFN-I production and generate a pro-inflammatory interplay that may stimulate the patient's anti-tumor immune response. Competing Interests: FT and JFF are authors of patents on MV. FT owns equity in Oncovita, an oncolytic virotherapy company. (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
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