Abstract
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.
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Data availability
All data are included in the Supplementary Information or available from the authors, as are unique reagents used in this Article. The raw numbers for charts and graphs are available in the Source Data file whenever possible. The single-cell RNA-seq data have been deposited in Genome Sequence Archive (GSA) database under the PRJCA038841 [https://ngdc.cncb.ac.cn/gsa/browse/CRA024829]. The MALDI-TOF data have been deposited in iProX database under the PXD063226 [https://www.iprox.cn//page/project.html?id=IPX0011728000]. The FACS data have been deposited in Flow Repository under the FR-FCM-Z9G8. Source data are provided with this paper.
Code availability
No software or algorithm was generated in this study. The analysis codes have been uploaded to GitHub, https://github.com/Qi-1111/BNCT_scripts.
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Acknowledgements
This study was funded by the National Natural Science Foundation of China (22225603, 22441051, and 22406006), the Ministry of Science and Technology of the People’s Republic of China (2021YFA1601400), the New Cornerstone Science Foundation (The XPLORER PRIZE), Changping Laboratory, the Basic Research Project of China National Nuclear Corporation (CNNC-JCYJ-202214), and Joint Funds for Regional Innovation and Development of the National Natural Science Foundation of China (U24A20732) to Z.L. We thank the facility support from the flow cytometry Core at national Center for Protein Sciences, and Analytical Instrumentation Centre at Peking University. The authors are grateful to Dr. Mo Hu and Dr. Lingxiao Chaihu (Mass Spectrometry Core, Changping Laboratory, China) for helpful discussion and technical assistance.
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Z.L. conceived the study. Q.S, assisted by S.Q. and K.W., performed BNCT experiment, cell studies and animal studies. Y.Z., under the guidance of Z.Z., performed the analysis of sc-RNA seq. Q.S, assisted by C.L., performed boron concentration analysis by ICP-MS. Z.Z. and T.L. provided thermal neutron source and performed SERA simulation. Q.S., assisted by S.Q., K.W., Z.G., Z.D., C.W. and J.L., performed all other experiments. Q.S, assisted by Y.Z., analyzed the data. Q.S. wrote the manuscript with inputs from all authors. All authors discussed the results and commented on the manuscript.
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Nature Communications thanks Shinji Kawabata, Luigi Ombrato and the other anonymous reviewer(s) for their contribution to the peer review of this work. A peer review file is available.
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Sun, Q., Zhao, Y., Qiao, S. et al. Boron neutron capture therapy preserves immune cells and induces robust anti-tumour immunity in preclinical mouse model. Nat Commun (2026). https://doi.org/10.1038/s41467-025-67984-y
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DOI: https://doi.org/10.1038/s41467-025-67984-y
