Intratumoral co-activation of ERV transcription and RNA virus-sensing is associated with radiotherapy-induced immune response and abscopal effect
10 affiliations
- 1Biomedical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- 2Izmir Biomedicine and Genome Center, Izmir, Turkey
- 3Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, Turkey
- 4Department of Physics and Astronomy, Heidelberg University, Heidelberg, Germany
- 5Institute of Computer Science, University of Tartu, Tartu, Estonia
- 6Institute of Molecular Oncology, Philipps-University, Marburg, Germany
- 7German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center (UGMLC), Marburg, Germany
- 8Genomics Core Facility, Philipps-University, Marburg, Germany
- 9Institute for Lung Health (ILH), Justus Liebig University, Giessen, Germany
- 10Institute of Translational Medicine for Health Care Systems, Medical School Berlin, Hochschule Für Gesundheit Und Medizin, Berlin, Germany
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.
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BibTeX
@article{logotheti2026intratumoral,
title = {{Intratumoral co-activation of ERV transcription and RNA virus-sensing is associated with radiotherapy-induced immune response and abscopal effect}},
author = {Stella Logotheti and Elif Yıldız and Sarah Hasan and Viktoriia Bulanova and Elpida Theodoridou and Stefan Kuhn and Thorsten Stiewe and Stephan Marquardt and Athanasia Pavlopoulou and Joao Seco},
journal = {NPJ Precision Oncology},
year = {2026},
month = oct,
doi = {10.1038/s41698-026-01715-4},
url = {https://doi.org/10.1038/s41698-026-01715-4},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Intratumoral co-activation of ERV transcription and RNA virus-sensing is associated with radiotherapy-induced immune response and abscopal effect
AU - Stella Logotheti
AU - Elif Yıldız
AU - Sarah Hasan
AU - Viktoriia Bulanova
AU - Elpida Theodoridou
AU - Stefan Kuhn
AU - Thorsten Stiewe
AU - Stephan Marquardt
AU - Athanasia Pavlopoulou
AU - Joao Seco
PY - 2026
DA - 2026/10/13
JO - NPJ Precision Oncology
DO - 10.1038/s41698-026-01715-4
UR - https://doi.org/10.1038/s41698-026-01715-4
AB - 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.
SN - 2397-768X
ER -