Immunotherapy enhances the risk of tumor oxidative stress and metastasis in lung cancer with radiation pneumonitis.

ABSTRACT: Radiation pneumonitis (RP) is a prevalent complication associated with lung cancer radiotherapy; nonetheless, its effects on lung cancer immunotherapy and the underlying biological mechanisms remain inadequately elucidated. Utilizing mouse models of RP and orthotopically lung cancer, we witnessed immunotherapy-enhanced liver metastasis of lung cancer within the context of RP, accompanied by increased neutrophil infiltration of the primary tumor. Analysis of metabolic adaptations driven by the inflammatory microenvironment during treatment revealed that RP and immunotherapy act synergistically to exacerbate lipid metabolic dysregulation and oxidative stress. Integrating clinical validation with single-cell RNA sequencing data from a multicenter lung adenocarcinoma cohort, we demonstrated th

SUBMITTER: Jiao R 

PROVIDER: S-EPMC12328386 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature