Bystander and abscopal effects of boron neutron capture therapy: radiobiological mechanisms and immunotherapeutic strategies.

Boron neutron capture therapy (BNCT) is a high-linear energy transfer radiotherapy that enables cell-scale selective tumor killing and has shown clinical potential in recurrent and radioresistant cancers. While most BNCT research has focused on boron delivery, dosimetry, and direct local cytotoxicity, accumulating evidence suggests that BNCT can also elicit non-targeted biological responses beyond the irradiated volume. In this review, we summarize experimental and emerging clinical evidence indicating that localized BNCT induces both bystander and abscopal effects, manifested as biological alterations in neighboring non-irradiated cells and growth suppression of distant tumors. We further integrate these phenomena within a radiation immunology framework, proposing that high-linear energy transfer (high-LET)-induced immunogenic cell death, accompanied by the release of tumor antigens and damage-associated molecular patterns (DAMPs), reshapes the tumor immune microenvironment and drives systemic antitumor immune responses that mechanistically link bystander and abscopal effects. On this basis, we discuss the rationale for combining BNCT with immunotherapeutic approaches, positioning BNCT not only as a precision local radiotherapy but also as a potential trigger of systemic radio-immunological effects. This integrated perspective provides a conceptual framework for future mechanistic studies and the rational design of BNCT-based combination strategies.