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

Tiphaine Delaunay; Mathilde Violland; Nicolas Boisgerault; Soizic Dutoit; Virginie Vignard; Christian Münz; Monique Gannage; Brigitte Dréno; Kristine Vaivode; Dace Pjanova; Nathalie Labarrière; Yaohe Wang; E Antonio Chiocca; Fabrice Le Boeuf; John C Bell; Philippe Erbs; Frédéric Tangy; Marc Grégoire; Jean-François Fonteneau

doi:10.1080/2162402X.2017.1407897

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

Oncoimmunology. 2017 Dec 26;7(3):e1407897. doi: 10.1080/2162402X.2017.1407897. eCollection 2018.

Authors

Tiphaine Delaunay^{1

2}, Mathilde Violland^{1

2}, Nicolas Boisgerault^{1

2}, Soizic Dutoit^{1

2}, Virginie Vignard^{1

2}, Christian Münz³, Monique Gannage^{3

4}, Brigitte Dréno^{1

2

5}, Kristine Vaivode⁶, Dace Pjanova⁶, Nathalie Labarrière^{1

2}, Yaohe Wang^{7

8}, E Antonio Chiocca⁹, Fabrice Le Boeuf^{10

11}, John C Bell^{10

11}, Philippe Erbs¹², Frédéric Tangy¹³, Marc Grégoire^{1

2}, Jean-François Fonteneau^{1

2}

Affiliations

¹ CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, France.
² Labex IGO, Immunology Graft Oncology, Nantes, France.
³ Institute of Experimental Immunology, University of Zürich, Switzerland.
⁴ School of Medicine, University of Geneva, Switzerland.
⁵ Dermatology Department, Nantes Hospital, Nantes, France.
⁶ Latvian Biomedical Research and Study Centre, Riga, Latvia.
⁷ Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
⁸ National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Zhengzhou University, China.
⁹ Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
¹⁰ Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Canada.
¹¹ University of Ottawa, Ottawa, Canada.
¹² Transgene, Illkirch, France.
¹³ Unité de Génomique Virale et Vaccination, Institut Pasteur, CNRS UMR-3569, Paris, France.

Abstract

Oncolytic immunotherapy using oncolytic viruses (OV) has been shown to stimulate the antitumor immune response by inducing the release of tumor-associated 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-1^neg/HLA-DP4^pos melanoma cells with NY-ESO-1^pos/HLA-DP4^neg melanoma cells infected and killed by different OV induces an intercellular transfer of NY-ESO-1 that allows the recognition of NY-ESO-1^neg/HLA-DP4^pos 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: CD4+ T Lymphocytes; Melanoma; Oncolytic Viruses; Oncolytic immunotherapy; Tumor-Associated Antigens.

Publication types

Research Support, Non-U.S. Gov't

Grants and funding

MR/M015696/1/MRC_/Medical Research Council/United Kingdom