质子束疗法通过依赖HMGB1的信号传导诱导保护性免疫
Jialing Wen1, Xuanzhang Tu1, Wangcai Ren2
1Department of Nuclear Physics, China Institute of Atomic Energy, Beijing, China.
Frontiers in public health
|February 5, 2026
概括
高剂量的质子束疗法通过诱导高流动性组盒1 (HMGB1) 释放,一种关键的损伤相关分子模式 (DAMP) 来触发远距离瘤的排斥. 这一发现澄清了质子疗法.
科学领域:
- 辐射瘤学 辐射瘤学
- 癌症免疫学 癌症免疫学
- 分子生物学分子生物学
背景情况:
- 传统的放射治疗可以抑制原发性瘤,并通过损伤相关分子模式 (DAMPs) 促进远程瘤免疫性.
- 质子束疗法在诱导DAMPs和增强免疫性方面的作用尚不清楚.
- 研究质子束疗法对DAMP的影响对于了解其免疫机制至关重要.
研究的目的:
- 为了研究质子束诱导的DAMP对远距离瘤殖民的影响.
- 为了确定最佳的质子束剂量来增强DAMPs在结肠癌细胞中的表达.
- 阐明质子束疗法的抗瘤作用背后的免疫机制.
主要方法:
- 在体外的细胞辐射实验以确定DAMPs表达的最佳质子剂量.
- 携带瘤的小鼠模型,以评估质子束在抑制远端瘤殖民化的有效性.
- 针对与DAMP相关的分子 (CRT,HMGB1) 的shRNA,以评估免疫反应和机制.
主要成果:
- 高剂量的质子辐射显著诱导高流动性组盒1 (HMGB1) 释放,但不是calreticulin (CRT) 膜暴露.
- HMGB1倒置显著减少了60%的远端瘤排斥,而CRT倒置则减少了20%的排斥.
- 高剂量的质子辐射会通过一个依赖于HMGB1的途径触发远端瘤殖民的拒绝.
结论:
- 质子束疗法,特别是高剂量,可以通过HMGB1释放诱导免疫细胞死亡 (ICD).
- HMGB1在质子诱导的ICD和远程瘤殖民的拒绝中发挥着主导作用.
- 这项研究促进了对质子束疗法的免疫机制的理解,为改善癌症治疗提供了见解.
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