Boron neutron capture therapy preserves immune cells and induces robust anti-tumour immunity in preclinical mouse model

Radiotherapy can both activate and suppress immunity, making it difficult to predict or modulate these opposing effects for better cancer treatment. Boron neutron capture therapy (BNCT), a cellular-level radiotherapy, has demonstrated remarkable therapeutic efficacy in clinical practice, but mechanistically remains inadequately explored. Here, we compare the effects of BNCT with X-ray irradiation at equivalent radiation doses on immune cells and define the immunological mechanisms behind the improved therapeutic benefit of BNCT in mouse tumour models. We find that BNCT has a minimal effect on immune cell viability, while it triggers an immunogenic tumour cell death, ultimately inducing stronger anti-tumour immunity. Additionally, single-cell RNA sequencing indicates that BNCT reshapes the tumour microenvironment by enhancing dendritic cells, T cells, and NK cells activity. Thus, these findings provide important insights into radiobiological mechanisms following BNCT and inform strategies to preserve immune cells during radiotherapy and to increase cancer treatment efficacy. The response of different immune cell subsets to radiation therapy (RT) greatly influences treatment outcome. Here, the authors compare the effects of RT and Boron neutron capture therapy (BNCT) in preclinical mouse models of melanoma and colorectal cancer, and show that BNCT achieves tumor cell-selective killing while preserving immune cell functions, allowing sustained anti-tumor immunity and long-term memory.