Tumor cells dying after cytotoxic therapy are a potential source of antigen for T-cell priming. Antigen-presenting cells (APC) can cross-present MHC I restricted peptides following uptake of dying cells. Depending on the nature of the surrounding environmental signals APC then orchestrate a spectrum of responses ranging from immune activation to inhibition. Previously, we have demonstrated that combining radiation with either agonistic anti-CD40 monoclonal antibody (mAb) or a systemically administered TLR-7 agonist can enhance CD8 T-cell dependent protection against syngeneic murine lymphoma models. However, it remains unknown how individual APC populations impact on this anti-tumor immune response. Using APC depletion models we demonstrate that dendritic cells (DC) but not macrophages or B cells are responsible for the generation of long-term immunological protection following combination therapy with radiotherapy (RT) and either anti-CD40 mAb or systemic TLR-7 agonist therapy. Novel immunotherapeutic approaches that augment antigen uptake and presentation by DC may further enhance the generation of therapeutic anti-tumor immune responses leading to improved outcome following RT.
- Received October 16, 2015.
- Revision received February 26, 2016.
- Accepted March 21, 2016.
- Copyright ©2016, American Association for Cancer Research.