Abstract B1: Radiotherapy promotes tumor-specific effector CD8+ T cells via DC activation.

Abstract

Abstract Radiotherapy is an important treatment for cancer. The main mode of action is thought to be the irreversible damage to tumor cell DNA, but there is evidence that irradiation mobilizes tumor-specific immunity and recent studies showed that the efficacy of high-dose radiotherapy depends on the presence of CD8+ T cells. We show here that the efficacy of radiotherapy given as a single, high dose (10 Gy) crucially depends on dendritic cells and CD8+ T cells, whereas CD4+ T cells or macrophages are dispensable. We show that local high-dose irradiation results in activation of tumor-associated dendritic cells that in turn support tumor-specific effector CD8+ T cells, thus identifying the mechanism that underlies radiotherapy-induced mobilization of tumor-specific immunity. We propose that – in the absence of irradiation – the activation status of dendritic cells rather than the amount of tumor-derived antigen is the bottleneck, which precludes efficient anti-tumor immunity. Citation Format: Anurag K. Gupta, Hans Christian Probst, Van Vuong, Alexandro Landshammer, Sabine Muth, Hideo Yagita, Reto Schwendener, Martin Pruschy, Alexander Knuth, Maries van den Broek. Radiotherapy promotes tumor-specific effector CD8+ T cells via DC activation. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B1.