FLASH radiation therapy mitigates immunogenic and pro-fibrotic transcriptomic responses in healthy lung tissue
Adrien Arrigo1, Louize Brants1, Verdi Vanreusel1
1Antwerp Research in Radiation Oncology (AReRO), Center for Oncological Research (CORE), University of Antwerp, Wilrijk, Antwerp, Belgium.
Summary
FLASH radiation therapy (RT) avoids lung damage by preventing inflammatory gene activation seen with conventional RT. This novel approach reduces acute chemokine enrichment and sustained macrophage-related gene expression.
Area of Science:
- Oncology
- Radiation Oncology
- Molecular Biology
Background:
- Lung damage is a common side effect of conventional radiation therapy (RT).
- FLASH RT, a novel ultra-high dose-rate radiation technique, shows potential for reducing normal tissue toxicity.
- The underlying mechanisms by which FLASH RT mitigates lung damage remain unclear.
Purpose of the Study:
- To elucidate the molecular mechanisms behind the lung-protective effects of FLASH radiation therapy (RT).
- To compare the transcriptional response of lung tissue to FLASH RT versus conventional dose-rate RT.
Main Methods:
- Bulk RNA-sequencing was performed on lung tissue at 24 hours and 2 weeks post-irradiation.
- Gene expression profiles were analyzed to identify differences between FLASH RT and conventional RT groups.
Main Results:
- FLASH RT did not induce acute chemokine enrichment, unlike conventional RT.
- NFKB1 upregulation, associated with inflammation, was not observed with FLASH RT.
- FLASH RT prevented sustained activation of genes involved in macrophage activation, chemotaxis, and differentiation.
Conclusions:
- FLASH RT minimizes lung damage by suppressing acute inflammatory responses and chronic macrophage-related gene activation.
- The distinct transcriptional profile induced by FLASH RT offers a molecular explanation for its lung-protective properties.
- These findings support the potential of FLASH RT as a safer alternative for cancer treatment, reducing radiation-induced lung injury.
