期刊
JOURNAL OF THORACIC ONCOLOGY
卷 15, 期 5, 页码 827-842出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jtho.2019.12.128
关键词
Oncolytic immunotherapy; Measles virus; Type I interferon; Gene homozygous deletion; Mesothelioma
资金
- La Ligue Regionale Grand Ouest contre le Cancer [CSIRGO: CD16, CSIRGO: CD22, CSIRGO: CD41, CSIRGO: CD44, CSIRGO: CD49, CSIRGO: CD72, CSIRGO: CD79, CSIRGO: CD85]
- La Ligue Nationale contre le Cancer, L'association [ARSMESO44]
- La Fondation du Souffle et le Fonds de Dotation Recherche en Sante Respiratoire
- La fondation ARC
- La Fondation pour la Recherche Medicale (FRM)
- L'Agence Nationale pour la Recherche [ANR-16CE18-0016]
- bourse Roche de Recherche 2015 en Oncologie Thoracique
- INSERM
- LabEX IGO program - National Research Agency through the investment of the future program [ANR-11-LABX-001601]
- Ligue Contre le Cancer
- Canceropole Region Ile-de-France
Introduction: Oncolytic immunotherapy is based on the use of nonpathogenic replicative oncolytic viruses that infect and kill tumor cells exclusively. Recently, we found that the spontaneous oncolytic activity of the Schwarz strain of measles virus (MV) against human malignant pleural mesothelioma (MPM) depends on defects in the antiviral type I interferon (IFN-I) response in tumor cells. Methods: In this study, we studied three independent human MPM bio-collections to identify the defects in the IFN-I responses in tumor cells. Results: We show that the most frequent defect is the homozygous deletions (HDs) of all the 14 IFN-I genes (IFN-alpha and IFN-beta) that we found in more than half of MV-sensitive MPM cell lines. These HDs occur together with the HDs of the tumor suppressor gene CDKN2A also located in the 9p21.3 chromosome region. Therefore, the IFN-I-/- MPM cell lines develop a partial and weak IFN-I response when they are exposed to the virus compared with that of normal cells and MV-resistant MPM cell lines. This response consists of the expression of a restricted number of IFN-stimulated genes that do not depend on the presence of IFN-I. In addition, the IFN-I- /- MPM cell lines infected by MV also develop a pro-inflammatory response associated with stress of the endoplasmic reticulum. Conclusion: Our study emphasizes the link between HDs of IFN-I encoding genes and the CDKN2A gene in MPM and sensitivity to MV oncolytic immunotherapy. (C) 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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