Work

Intratumoral co-activation of ERV transcription and RNA virus-sensing is associated with radiotherapy-induced immune response and abscopal effect

Year: 2026

Type: article

Abstract: Radiotherapy (RT) transforms tumors into in situ vaccines that trigger antitumor immunity. However, the relevant pathways remain largely unelucidated, limiting clinical translation. Herein, we developed a hybrid dry-lab/wet-lab approach integrating systems-level immune phenotypes following homogenous or spatially fractionated RT (SFRT) with transcriptomic profiling of irradiated tumors. By combining feature extraction with machine-learning, including multilayer perceptron modeling, we ranked predictors of immune infiltration and patient survivability for each RT type. RT induced coordinated upregulation of viral RNA-binding proteins (OASes and RIG I-like receptors) along with endogenous retrovirus (ERV) RNAs predominately 400–800 bp long, which may serve as their ligands. During abscopal responses, OASes and ERV transcripts were co-induced and shared between irradiated and distant tumors. SFRT triggered earlier activation of OAS signaling versus homogenous RT. Our findings highlight ERVs as underappreciated contributors to RT-induced antitumor immunity and their interactions with intratumoral cytosolic sensors as potential novel biomarkers in precision radio-oncology.

Source: npj Precision Oncology

DOI: 10.1038/s41698-026-01715-4