OSCR

PARP7 inhibition and a STING agonist potentiate radiation-induced immunogenicity in glioblastoma.

Overview

Authors: Luca Lippert1,2,3,4,5, Ava Kleinwächter1,2,4,5,6, Anna Ohradanova-Repic7, Filip Horvat1,2,4,5, Lisa-Marie Appel1,2,4,5, Lena Walch1,2,4,5, Niccolò Bragato1,2,3, Jakob Wimmer1,2,3, Hanna Wopfner1,2,3,4,5, Anna Röhrer1,2,3, Magdalena Engl1,2,4,5,6, Kapil Upadhyaya8, Joachim Widder1,2, Michael S Cohen8, Dea Slade1,2,3,4,5
ORCID iDs: Luca Lippert, Anna Ohradanova-Repic, Lisa-Marie Appel, Niccolò Bragato, Joachim Widder, Dea Slade
  1. Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria
  2. Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  3. MedAustron Ion Therapy Center, Wiener Neustadt, Austria
  4. Max Perutz Labs, Vienna Biocenter Campus (VBC), Vienna, Austria
  5. Medical University of Vienna, Center for Medical Biochemistry, Vienna, Austria
  6. Vienna Biocenter PhD Program, A Doctoral School of the University of Vienna and the Medical University of Vienna, Vienna, Austria
  7. Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria
  8. Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, OR, USA
Institutions: Max Perutz Labs (Austria); Comprehensive Cancer Center Vienna (Austria); Vienna Biocenter (Austria); MedAustron (Austria); Medical University of Vienna (Austria); University of Vienna (Austria); Oregon Health & Science University (United States)
Journal: Oncoimmunology, volume 15, issue 1, article 2656053
Dates: received 26 May 2025; accepted 1 April 2026; published online 14 April 2026; in print December 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1080/2162402x.2026.2656053 · PMID 41979168 · PMCID PMC13081750 · OpenAlex W7154201665
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), mouse (organism), other condition (population), cellular / molecular (subfield)
Methods: Connectivity, Statistics, Evoked potentials, fMRI & imaging
Keywords: Glioblastoma, radiation, PARP7, STING agonist, IFN-I response
MeSH: Brain Neoplasms*, Glioblastoma*, Membrane Proteins*, Poly(ADP-ribose) Polymerase Inhibitors*, Animals, Cell Line, Tumor, cGAS-STING Signaling Pathway, Humans, Interferon Type I, Mice, Neoplastic Stem Cells, Signal Transduction, STING Protein, Tumor Microenvironment (* major topic)
Topic: interferon and immune responses (Immunology, Immunology and Microbiology), according to OpenAlex
Funding: Austrian Science Fund FWF (P 34253)
Citations: cited by 2 papers (Europe PMC); 109 references in the paper

Abstract

Glioblastoma (GBM) is the most lethal form of brain cancer with an immunosuppressive tumor microenvironment (TME). Radio- and chemotherapy can modify the TME and elicit anti-tumor immunity through the STING and type I interferon (IFN-I) pathways. STING agonists or DNA damage response inhibitors can potentiate the effects of radiation by targeting the IFN-I pathway. Here, we examined the immunogenic response of GBM cells to hypofractionated or single-dose radiation combined with a STING agonist or inhibitors targeting immune signaling (PARP7), the DNA damage response, cell cycle checkpoints or autophagy. We found that hypofractionated radiation elicited a ferroptosis-dependent IFN-I response and that the PARP7 inhibitor KMR-206 and the STING agonist diABZI enhanced the effects of radiation by activating immune cells. In patient-derived GBM cancer stem cells with low STING levels, the PARP7 inhibitor was more effective at inducing immunogenic signaling compared to the STING agonist. Our results highlight the potential of PARP7 inhibitors as a new treatment to boost anti-tumor immunity in GBM, which may be more advantageous compared to STING agonists given that STING is often downregulated in GBM.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

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Data

Datasets cited

Data availability statement

The RNA-seq data that support the findings of this study are openly available in Array Express at https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-14858?key=fe296ac5-b9e9-4e67-846c-1e9f756c30eb, accession number: E-MTAB-14858. The raw data files (uncropped western blots, western blot quantifications and data points for all replicates shown in the graphs) are provided in Supplementary Data 3 (for the main figures) and Supplementary Data 4 and 5 (for Supplementary figures). Any other information is available from the corresponding author upon request.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 5 keywords, 14 MeSH terms, 1 funder, 109 references.

Cite

This paper

Lippert, L., Kleinwächter, A., Ohradanova-Repic, A., Horvat, F., Appel, L.-M., Walch, L., Bragato, N., Wimmer, J., Wopfner, H., Röhrer, A., Engl, M., Upadhyaya, K., Widder, J., Cohen, M. S., & Slade, D. (2026). PARP7 inhibition and a STING agonist potentiate radiation-induced immunogenicity in glioblastoma. Oncoimmunology, 15(1), 2656053. https://doi.org/10.1080/2162402x.2026.2656053

BibTeX

@article{lippert2026parp7,
author = {Lippert, Luca and Kleinwächter, Ava and Ohradanova-Repic, Anna and Horvat, Filip and Appel, Lisa-Marie and Walch, Lena and Bragato, Niccolò and Wimmer, Jakob and Wopfner, Hanna and Röhrer, Anna and Engl, Magdalena and Upadhyaya, Kapil and Widder, Joachim and Cohen, Michael S and Slade, Dea},
title = {{PARP7 inhibition and a STING agonist potentiate radiation-induced immunogenicity in glioblastoma}},
journal = {Oncoimmunology},
year = {2026},
month = apr,
volume = {15},
number = {1},
pages = {2656053},
publisher = {Taylor \& Francis},
issn = {2162-4011},
doi = {10.1080/2162402x.2026.2656053},
url = {https://doi.org/10.1080/2162402x.2026.2656053},
pmid = {41979168},
pmcid = {PMC13081750}
}

RIS

TY - JOUR
AU - Lippert, Luca
AU - Kleinwächter, Ava
AU - Ohradanova-Repic, Anna
AU - Horvat, Filip
AU - Appel, Lisa-Marie
AU - Walch, Lena
AU - Bragato, Niccolò
AU - Wimmer, Jakob
AU - Wopfner, Hanna
AU - Röhrer, Anna
AU - Engl, Magdalena
AU - Upadhyaya, Kapil
AU - Widder, Joachim
AU - Cohen, Michael S
AU - Slade, Dea
TI - PARP7 inhibition and a STING agonist potentiate radiation-induced immunogenicity in glioblastoma
T2 - Oncoimmunology
J2 - Oncoimmunology
PY - 2026
DA - 2026/04/14
VL - 15
IS - 1
SP - 2656053
SN - 2162-4011
PB - Taylor & Francis
DO - 10.1080/2162402x.2026.2656053
UR - https://doi.org/10.1080/2162402x.2026.2656053
LA - en
ER -

CSL-JSON

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