Type I Interferon Response in Radiation-Induced Anti-Tumor Immunity

The anti-tumor activity of interferons (IFNs) was first appreciated about half a century ago, and IFN-α2 was the first cancer immunotherapy approved by the US Food and Drug Administration. Radiation therapy (RT), one of the pillars of cancer treatment, directly causes DNA damage, which can lead to senescence and cell death in tumor cells. In recent years, however, RT-induced immunomodulatory effects have been recognized to play an indispensable role in achieving the optimum therapeutic effect of RT. Increasing evidence indicates that RT enhances adaptive anti-tumor immunity by augmenting the innate immune sensing of tumors in a type I IFN-dependent matter. This review briefly introduces the role of type I interferon in cancer and the available evidence on the overall effects of RT on tumor immunity mediated via type I IFN. Recent advances in deciphering the molecular mechanisms underlying the induction of type I IFNs triggered by RT, their clinical implications, and therapeutic opportunities will be highlighted.