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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Inflammation

This article is part of the Research TopicInflammation, Immunity, and Cancer: New Pathways Towards Therapeutic InnovationView all 35 articles

Amplifying radiation-induced anti-tumor immunity: the dual role of brachytherapy and low-dose total body irradiation

Provisionally accepted
Yingqi  GuYingqi Gu1*Yang  YangYang Yang1Jian  GaoJian Gao1ZhouXue  WuZhouXue Wu1Jia  WangJia Wang1Chen  XieChen Xie2XinYi  WangXinYi Wang1Min  WuMin Wu1YunXue  ZhengYunXue Zheng1XiaoYin  ZhangXiaoYin Zhang1Yue  ChenYue Chen1ShaoZhi  FuShaoZhi Fu1Wu  Jing BoWu Jing Bo1
  • 1The Affiliated Hospital of Southwest Medical University, Luzhou, China
  • 2Luzhou People's Hospital, Luzhou, China

The final, formatted version of the article will be published soon.

Background: Radiotherapy can be a vaccine by triggering patients' prophylactic tumor-specific immune responses. Brachytherapy has biological and physical benefits over external beam radiation. Low-dose total body irradiation can produce systemic immunity. We hypothesized that brachytherapy more effectively modulates immunity than external beam radiotherapy, with low-dose whole-body irradiation amplifying this effect. Methods: After creating the Lewis lung cancer model, we compared hypo-fractionated brachytherapy with hypo-fractionated radiotherapy, examining immunogenic cell death, DNA damage, cell proliferation and immune cells in tumor. We then evaluated if low-dose whole-body irradiation could boost hypo-fractionated brachytherapy's systemic immunomodulatory effects and trigger a distant response. Results: Hypo-fractionated brachytherapy was more effective in inhibiting tumor growth than external beam radiotherapy. Hypo-fractionated brachytherapy approach significantly influenced various immune cells within the tumor microenvironment, including T cells, DC cells, NK cells, MDSC cells, tumor-associated macrophages. Furthermore, low-dose whole-body irradiation at 0.1 Gy augmented the immunological effects of low-fractionation brachytherapy and elicited transient systemic immune activation in mice. Conclusions: Our research indicates that brachytherapy offers superior immune modulation over external radiotherapy. When combined with low-dose total body irradiation, it transiently activates the systemic immune response.

Keywords: Hypo-fractionated brachytherapy, hypo-fractionated radiotherapy, Immunogenic cell death, low-dose total body irradiation, systemic immune related response

Received: 19 Dec 2025; Accepted: 27 Jan 2026.

Copyright: © 2026 Gu, Yang, Gao, Wu, Wang, Xie, Wang, Wu, Zheng, Zhang, Chen, Fu and Bo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yingqi Gu

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