Radiation-induced bystander and abscopal effects: important lessons from preclinical models

International audienceRadiotherapy is a pivotal component in the curative treatment of patients with localised cancer and isolated metastasis, as well asbeing used as a palliative strategy for patients with disseminated disease. The clinical efficacy of radiotherapy has traditionally beenattributed to the local effects of ionising radiation, which induces cell death by directly and indirectly inducing DNA damage, butsubstantial work has uncovered an unexpected and dual relationship between tumour irradiation and the host immune system. Inclinical practice, it is, therefore, tempting to tailor immunotherapies with radiotherapy in order to synergise innate and adaptiveimmunity against cancer cells, as well as to bypass immune tolerance and exhaustion, with the aim of facilitating tumourregression. However, our understanding of how radiation impacts on immune system activation is still in its early stages, andconcerns and challenges regarding therapeutic applications still need to be overcome. With the increasing use of immunotherapyand its common combination with ionising radiation, this review briefly delineates current knowledge about the non-targetedeffects of radiotherapy, and aims to provide insights, at the preclinical level, into the mechanisms that are involved with thepotential to yield clinically relevant combinatorial approaches of radiotherapy and immunotherap