At the heart of the primary lesion that is irradiated (panel on the left), two local effects can be distinguished: first, bystander effects occur between high-dose-targeted cells (dark orange) or low-dose-targeted cells (light orange) and non-irradiated cells (blue); second, cohort effects occur between high-dose-targeted cells and low-dose-targeted cells. Whether/how non-irradiated cells can influence the outcome of irradiated cells (depicted with a question mark) remains to be determined. Irradiation induces immunogenic cell death in cancer cells and the subsequent release of tumour-associated antigens (TAAs) (pink dots), thereby activating the immune system, especially antigen-presenting cells (APC, in purple) and macrophages (in pink). APCs then cross-present TAAs to T cells in draining lymph nodes. As a result, polyclonal antigen-specific T cells are primed to attack tumours located within the irradiated field as well as those in distant locations. This distant radiation-induced effect is termed an abscopal effect (panel on the right). Exosomes (in green) are novel mediators thought to participate in these non-targeted effects locally and at distant sites.
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