Evidence map›Paper›PMID 38941297›Full record

ArticleThe Journal of clinical investigation2024

STING agonist 8803 reprograms the immune microenvironment and increases survival in preclinical models of glioblastoma.

Hinda Najem, Spencer T Lea, Shashwat Tripathi, Lisa Hurley, Chao-Hsien Chen, Ivana William, Moloud Sooreshjani, Michelle Bowie, Genevieve Hartley, Corey Dussold and 21 more

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing 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

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

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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

31 authors.

Hinda NajemDepartment of Neurological Surgery and.
Spencer T LeaDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Shashwat TripathiDepartment of Neurological Surgery and.
Lisa HurleyDepartment of Neurological Surgery and.
Chao-Hsien ChenDepartment of Neurology, Houston Methodist Neurological Institute, Houston, Texas, USA.
Ivana WilliamDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Moloud SooreshjaniDepartment of Neurological Surgery and.
Michelle BowieDepartment of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Genevieve HartleyDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Corey DussoldDepartment of Neurological Surgery and.
Sebastian PachecoDepartment of Neurological Surgery and.
Crismita DmelloDepartment of Neurological Surgery and.
Catalina Lee-ChangDepartment of Neurological Surgery and.
Kathleen McCortneyDepartment of Neurological Surgery and.
Alicia SteffensDepartment of Neurological Surgery and.
Jordain WalshonDepartment of Neurological Surgery and.
Martina OttMiltenyi Biotec, Bergisch Gladbach, Germany.
Jun WeiDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Anantha MarisettyImmatics US, Houston, Texas, USA.
Irina BalyasnikovaDepartment of Neurological Surgery and.
Roger StuppDepartment of Neurological Surgery and.
Rimas V LukasMalnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Jian HuDepartment of Cancer Biology and.
Charles David JamesDepartment of Neurological Surgery and.
Craig M HorbinskiDepartment of Neurological Surgery and.
Maciej S LesniakDepartment of Neurological Surgery and.
David M AshleyDepartment of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Waldemar PriebeDepartment of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Leonidas C PlataniasRobert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Michael A CurranDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Amy B HeimbergerDepartment of Neurological Surgery and.

Funding

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
Development of B-cell-based vaccine for GlioblastomaR37CA258426 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Catalina Lee Chang · 2021 to 2026
$2.2M
Stinging the Glioma Immune LandscapeR01NS120547 · NINDS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HEIMBERGER, AMY BETH, RAO, ARVIND · 2020 to 2023
$1.1M
NCI NIH HHS P50 CA221747NCI NIH HHS R37 CA258426NCI NIH HHS T32 CA009560NINDS NIH HHS R01 NS120547
6 · The paper itself

Abstract

STING agonists can reprogram the tumor microenvironment to induce immunological clearance within the central nervous system. Using multiplexed sequential immunofluorescence (SeqIF) and the Ivy Glioblastoma Atlas, STING expression was found in myeloid populations and in the perivascular space. The STING agonist 8803 increased median survival in multiple preclinical models of glioblastoma, including QPP8, an immune checkpoint blockade-resistant model, where 100% of mice were cured. Ex vivo flow cytometry profiling during the therapeutic window demonstrated increases in myeloid tumor trafficking and activation, alongside enhancement of CD8+ T cell and NK effector responses. Treatment with 8803 reprogrammed microglia to express costimulatory CD80/CD86 and iNOS, while decreasing immunosuppressive CD206 and arginase. In humanized mice, where tumor cell STING is epigenetically silenced, 8803 therapeutic activity was maintained, further attesting to myeloid dependency and reprogramming. Although the combination with a STAT3 inhibitor did not further enhance STING agonist activity, the addition of anti-PD-1 antibodies to 8803 treatment enhanced survival in an immune checkpoint blockade-responsive glioma model. In summary, 8803 as a monotherapy demonstrates marked in vivo therapeutic activity, meriting consideration for clinical translation.

Indexed as

GlioblastomaMembrane ProteinsTumor MicroenvironmentAnimalsBrain NeoplasmsCell Line, TumorHumansMiceSTING ProteinMembrane ProteinsSTING1 protein, humanSting1 protein, mouseSTING ProteinBrain cancerCancer immunotherapyImmunologyOncologySignal transduction

Identifiers

PMID38941297
PMCPMC11178548

What OpenQuestion holds

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Registered trials

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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.