Anti-tumor efficacy of radiation and immunotherapy combinations is dependent on dendritic cell activation of effector CD8+ T-cells
Menée in vitro et à l'aide de modèles murins de lymphome à lymphocytes B ou T, cette étude montre que l'efficacité d'un traitement combinant radiothérapie et immunothérapie dépend de l'activation des lymphocytes T CD8+ par les cellules dendritiques
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.