Ghidini Antonio, Roncari Luisa, Bukovec Roberta, Garassino Isabella, Mastrelia Antonio, Petrelli Fausto
The abscopal effect refers to the regression of distant, untreated tumors following localized treatment of a primary lesion. First described by R.H. Mole in 1953, it was long considered a rare curiosity in radiation oncology. With the advent of immune checkpoint inhibitors, interest has resurged as an attainable clinical outcome. This review traces the historical development of the abscopal effect and examines the underlying immune-mediated mechanisms - including immunogenic cell death, cGAS-STING pathway activation, type I interferon production, dendritic cell maturation, and cytotoxic T cell priming. We survey clinical evidence across tumor types and treatment contexts, including radiotherapy alone, radiotherapy combined with checkpoint inhibitors, and other locoregional therapies such as cryoablation. Finally, we discuss translational implications: factors influencing occurrence, strategies to enhance abscopal responses, and ongoing trials. Although true abscopal responses remain unpredictable and relatively infrequent, understanding this phenomenon provides critical insights into tumor-immune interactions and holds promise for converting local therapies into in situ vaccines capable of driving systemic cancer control.