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Oncolytic viruses sensitize human tumor cells for NY-ESO-1 tumor antigen recognition by CD4+ effector T cells

Tiphaine Delaunay 1, 2 Mathilde Violland 1, 2 Nicolas Boisgerault 1, 2 Soizic Dutoit 1, 2 Virginie Vignard 3, 2 Christian Münz 4 Monique Gannagé 4, 5 Brigitte Dréno 6, 2, 7 Kristine Vaivode 8 Dace Pjanova 8 Nathalie Labarriere 3, 2 Yaohe Wang 9, 10 E Chiocca 11 Fabrice Le Boeuf 12, 13 John Bell 12, 13 Philippe Erbs 14 Frédéric Tangy 15 Marc Grégoire 1, 2 Jean-François Fonteneau 1, 2, *
* Corresponding author
1 CRCINA-ÉQUIPE 4 - Immunogenic Cell Death and Mesothelioma Therapy
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
2 LabEX IGO Immunothérapie Grand Ouest
3 CRCINA-ÉQUIPE 3 - Anti-Tumor Immunosurveillance and Immunotherapy
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
4 Institute of Experimental Immunology - IEI [Zürich, Switzerland]
5 School of Medicine [Geneva, Switzerland]
6 Service de dermatologie [Nantes]
7 CRCINA-ÉQUIPE 2 - Clinical and Translational Research in Skin Cancer
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
8 Latvian Biomedical Research and Study Centre [Rīga]
9 Centre for Molecular Oncology [London, UK]
10 National Centre for International Research in Cell and Gene Therapy [Henan Sheng, Chine]
11 Department of Neurosurgery - Harvey Cushing Neuro-Oncology Laboratories [Boston, USA]
12 Center for Innovative Cancer Therapeutics [Ottawa, Canada]
13 uOttawa - University of Ottawa [Ottawa]
14 Transgene SA [Illkirch]
15 Génomique virale et vaccination
Abstract : Oncolytic immunotherapy using oncolytic viruses (OV) has been shown to stimulate the antitumor immune response by inducing the release of tumorassociated antigens (TAA) and danger signals from the dying infected tumor cells. In this study, we sought to determine if the lysis of tumor cells induced by different OV: measles virus, vaccinia virus, vesicular stomatitis virus, herpes simplex type I virus, adenovirus or enterovirus, has consequences on the capacity of tumor cells to present TAA, such as NY-ESO-1. We show that the co-culture of NY-ESO-1neg/HLADP4pos melanoma cells with NY-ESO-1pos/HLA-DP4neg melanoma cells infected and killed by different OV induces an intercellular transfer of NY-ESO-1 that allows the recognition of NY-ESO-1neg/HLA-DP4pos tumor cells by an HLA-DP4/NY-ESO-1(157- 170)-specific CD4+ cytotoxic T cell clone, NY67. We then confirmed this result in a second model with an HLA-DP4+ melanoma cell line that expresses a low amount of NY-ESO-1. Recognition of this cell line by the NY67 clone is largely increased in the presence of OV productive infection. Altogether, our results show for the first time another mechanism of stimulation of the anti-tumor immune response by OV, via the loading of tumor cells with TAA that sensitizes them for direct recognition by specific effector CD4+ T cells, supporting the use of OV for cancer immunotherapy.
Keywords : Tumor-Associated Antigens CD4+ T Lymphocytes Melanoma Oncolytic immunotherapy Oncolytic Viruses
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https://www.hal.inserm.fr/inserm-01644345
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Submitted on : Wednesday, November 22, 2017 - 10:40:05 AM
Last modification on : Friday, October 23, 2020 - 4:45:43 PM

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Tiphaine Delaunay, Mathilde Violland, Nicolas Boisgerault, Soizic Dutoit, Virginie Vignard, et al.. Oncolytic viruses sensitize human tumor cells for NY-ESO-1 tumor antigen recognition by CD4+ effector T cells. OncoImmunology, Taylor & Francis, In press, ⟨10.1080/2162402X.2017.1407897⟩. ⟨inserm-01644345⟩

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