Immunogenic potential of irradiated lymphoma cells is enhanced by adjuvant immunotherapy and modulation of local macrophage populations

Abstract

The aim of this study was to assess the immunogenic potential of irradiated lymphoma cells in vivo and determine whether immunogenicity can be enhanced by modulation of the host immune system. Syngeneic murine lymphoma models irradiated ex vivo were used as an orthotopic cellular vaccination prior to challenge with viable tumor cells. We demonstrate that irradiated lymphoma cells are poorly immunogenic and that protective anti-tumor CD8 T-cell responses require the addition of immunostimulatory monoclonal antibody as an immune adjuvant, and increased frequency of antigen exposure by multiple vaccinations. Furthermore, we show the potential importance of macrophages in regulating immunogenicity of irradiated lymphoma cells and demonstrate that depletion of macrophages using clodronate-encapsulated liposomes considerably enhances primary vaccination efficacy in the presence of adjuvant anti-CD40 antibody. Our results demonstrate that the immunogenic potential of poorly immunogenic lymphoma cells dying after radiation therapy can be improved by modulation of the host immune system.

Keywords::

• Radiation
• anti-CD40
• vaccination
• macrophage
• lymphoma

Acknowledgements

We would like to thank all members of the Tenovus Research Laboratory for their help and advice. In particular we thank Prof. Martin Glennie, Richard Reid and Sam Martin for expert advice and technical assistance. Funding for this work was provided by Cancer Research UK and Leukaemia and Lymphoma Research.

Potential conflict of interest:

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