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

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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-1neg/HLA-DP4pos 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.

Original languageEnglish
Article numbere1407897
JournalOncoImmunology
Volume7
Issue number3
DOIs
StatePublished - 4 Mar 2018
Externally publishedYes

Keywords

  • CD4+ T Lymphocytes
  • Melanoma
  • Oncolytic Viruses
  • Oncolytic immunotherapy
  • Tumor-Associated Antigens

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