Evidence map›Paper›PMID 41697735›Full record

ArticleThe Journal of clinical investigation2026

STING-induced blood-brain barrier opening combined with radiotherapy potentiates antitumor response in a high-grade glioma model.

Shashwat Tripathi, Hinda Najem, Lisa Hurley, Ruochen Du, Crismita Dmello, Heba Ali, Kathleen McCortney, Karl J Habashy, Peng Zhang, Craig M Horbinski and 13 more

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Therapeutic targeting of the cGAS-STING pathway in human disease.The Journal of clinical investigation · 2026
    Review
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Shashwat TripathiDepartment of Neurological Surgery.
Hinda NajemDepartment of Neurological Surgery.
Lisa HurleyDepartment of Neurological Surgery.
Ruochen DuDepartment of Neurological Surgery.
Crismita DmelloDepartment of Neurological Surgery.
Heba AliDepartment of Neurological Surgery.
Kathleen McCortneyDepartment of Neurological Surgery.
Karl J HabashyDepartment of Neurological Surgery.
Peng ZhangDepartment of Neurological Surgery.
Craig M HorbinskiDepartment of Neurological Surgery.
Lara LeoniDepartment of Radiology.
Ryan J AveryDepartment of Radiology.
Rimas V LukasMalnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center.
Timothy L SitaMalnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center.
David R RaleighDepartment of Radiation Oncology, Neurological Surgery, and Pathology, University of California, San Francisco, San Francisco, California, USA.
Sean SachdevMalnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center.
Roger StuppDepartment of Neurological Surgery.
Maciej S LesniakDepartment of Neurological Surgery.
David M AshleyDepartment of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Daniele ProcissiDepartment of Radiology.
Michael A CurranDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Irina BalyasnikovaDepartment of Neurological Surgery.
Amy B HeimbergerDepartment of Neurological Surgery.

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Devalingam Mahalingam · 1993 to 2026
$153.9M
STINGing GBM: A First-in- Man Clinical Trial in Surgical Resectable Recurrent GBMP50CA221747 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Hui Zhang · 2018 to 2026
$21.4M
CARCINOGENESIS TRAINING PROGRAMT32CA009560 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Kathleen Janee Green · 1986 to 2026
$8.4M
State-of-the-art High Field 7T MRI System Upgrade to Accelerate Translational SciencesS10OD032221 · OD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MARKL, MICHAEL · 2023 to 2023
$1.5M
NCI NIH HHS P30 CA060553NCI NIH HHS P50 CA221747NCI NIH HHS T32 CA009560NIH HHS S10 OD032221
6 · The paper itself

Abstract

Radiation therapy (RT) is the standard of care for glioblastoma but is not curative. Triggering the cGAS/stimulator of interferon genes (STING) pathway with potent agonists, such as 8803, exerts activity across high-grade glioma preclinical models. To determine if the combination of 8803 with RT warrants consideration in the up-front treatment setting and to clarify the underlying mechanisms of therapeutic activity, C57BL/6J mice harboring intracerebral CT-2A or QPP8v gliomas were treated with RT, intratumoral 8803, or both. The treatment with the combination resulted in 80% long-term survival in the CT-2A model but not in the radiation-resistant QPP8v model. This therapeutic effect was maintained in Sting-/- CT-2A cells, highlighting the direct role of the immune system in mediating the survival benefit. Single-cell RNA-Seq identified increased nitric oxide synthase 2 (Nos2) in inflammatory tumor-associated macrophages; however, the therapeutic effect was maintained in Nos2-/- mice. Additionally, 8803 reprogrammed the blood-brain barrier (BBB) by altering the Pecam and Cd147 pathways in endothelial cells; intracranial injection of 8803 induced bihemispheric BBB opening for up to 24 hours. Sting activation was visualized longitudinally using 3'-deoxy-3'-[18F]-fluorothymidine ([18F]-FLT) PET, which peaked 72-96 hours after 8803 administration. In summary, 8803 combined with RT triggers distinctive antiglioma immune reactivity, facilitates BBB opening, and warrants consideration for up-front clinical trials in glioblastoma, where treatment effects can be monitored using [18F]-FLT PET imaging.

Indexed as

Blood-Brain BarrierBrain NeoplasmsGliomaMembrane ProteinsNeoplasm ProteinsNeoplasms, ExperimentalAnimalscGAS-STING Signaling PathwayDisease Models, AnimalHumansMiceMice, Inbred C57BLMice, KnockoutSTING ProteinMembrane ProteinsNeoplasm ProteinsSting1 protein, mouseSTING ProteinBrain cancerCancer immunotherapyImmunologyOncologyTherapeuticsVascular biology

Identifiers

PMID41697735
PMCPMC12904701

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.