ArticleCommunications medicine2026
The radiotherapy induced cyclic GMP-AMP-synthase re-localization and immune signature predicts HNSCC treatment efficacy.
Article in Communications medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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Who cites it
1 citing paper in PubMed.
- Reframing the paradigm: stereotactic body radiation therapy as an engineer of the tumor immune microenvironment.Frontiers in immunology · 2026Review
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Authors and funding
10 authors.
Funding
Abstract
backgroundRadiotherapy (RT) is a crucial treatment for head and neck squamous cell carcinoma (HNSCC). Recent pre-clinical studies highlight the potential of combining RT with immunotherapy due to RT-induced activation of the cyclic GMP-AMP-synthase (cGAS)/Stimulator of Interferon (IFN) Genes (STING) pathway, yet the clinical implications remain unclear.
methodsIn this study, we utilized a cGAS-mNeongreen knock-in tumor model, human HNSCC cell lines and serial tumor biopsies from HNSCC patients to investigate RT-induced cGAS activation and re-localization. cGAS positive micronuclei and IFN stimulated gene (ISG) induction were quantified. In HNSCC patient biopsies, cGAS positive micronuclei were identified in different cellular compartments and IFN/ISG and NF-κB serum levels were correlated to survival. Differences were tested using paired t-tests, Wilcoxon test, One-way and two-way ANOVA or Kaplan Meier curves.
resultsHere we show that cGAS positive foci present in micronuclei increase post-RT in both mouse tumor models (P = 0.0305; t-test) and HNSCC patient biopsies (P = 0.0012; Wilcoxon test), concurrently with higher ISG expression. Notably, cGAS re-localization in HNSCC patient biopsies is most prominent in immune cell-infiltrated tumor regions (P = 0.0061; Wilcoxon test). Enhanced systemic type I IFN inducing activity is observed post-RT (P = 0.0040; mixed-effects analysis) and correlates with improved survival (OS P = 0.0146; log-rank test; DFS P = 0.0256; Gehan-Breslow-Wilcoxon test), particularly in HPV positive patients (OS P = 0.0017; log-rank test; DFS P = 0.043; log-rank test).
conclusionsThese findings suggest that cGAS re-localization and systemic IFN responses may serve as biomarkers for RT efficacy, providing a basis for optimizing HNSCC treatment protocols, especially when integrated with immunotherapy.
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Registered trials
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