Abstract Purpose: Although radiotherapy (RT) is a predominant treatment for non-small cell lung cancer (NSCLC), radioresistance remains a major challenge and is strongly linked to dysregulated tumor immune microenvironments (TIME). Immunoradiotherapy has shown improved therapeutic activity by promoting antitumor immune responses and modifying the TIME. Recent studies positions STING activation as a potent catalyst of this immune reprogramming. Therefore, identifying upstream regulators capable of enhancing STING-mediated immune activation is critical for developing strategies to overcome radioresistance in NSCLC. Methods: Ubiquitin-specific protease3 (USP3) expression patterns, immune infiltration profiles, and pathway enrichment analyses were performed using public datasets and institutional sequencing data. Prognostic value was evaluated via TCGA datasets and validated in a clinical cohort of 105 NSCLC patients (Tianjin Medical University Cancer Institute Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6605.
Cheng et al. (Fri,) studied this question.