The Efficacy of Radiotherapy Relies upon Induction of Type I Interferon–Dependent Innate and Adaptive Immunity

The most widely held explanation for the efficacy of local radiotherapy (RT) is based on direct cytotoxicity to cancer cells through the induction of lethal DNA damage. Recent studies have shown that local ablative radiation of established tumors can lead to increased T-cell priming and T-cell-dependent tumor regression, but the underlying mechanism remains unclear. Here, we describe an essential role for type I IFN in local RT-mediated tumor control. We show that ablative RT increases intratumoral production of IFN-β and, more surprisingly, the antitumor effect of RT is abolished in type I IFN nonresponsive hosts. Furthermore, the major target of RT-induced type I IFN is the hematopoietic compartment. RT…