Evidence map›Paper›PMID 25300859›Full record

ArticleCancer immunology research2014

STING contributes to antiglioma immunity via triggering type I IFN signals in the tumor microenvironment.

Takayuki Ohkuri, Arundhati Ghosh, Akemi Kosaka, Jianzhong Zhu, Maki Ikeura, Michael David, Simon C Watkins, Saumendra N Sarkar, Hideho Okada

Open access · bronzeAbstract read
In one paragraph

Article in Cancer immunology research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
167citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 4% of its field
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

167 citing papers in PubMed, 1 synthesis or guideline pooled it, 256 citations in OpenAlex.

  1. Pooled it
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  18. cGAS-agonistic spherical nucleic acids reprogram the glioblastoma immune microenvironment and promote antitumor immunity.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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107 more citing papers are in PubMed but not listed here.

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

9 authors at 3 institutions in 1 country.

Takayuki OhkuriDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Department of Brain Tumor, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
Arundhati GhoshDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Cancer Virology Programs, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
Akemi KosakaDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Department of Brain Tumor, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
Jianzhong ZhuDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Cancer Virology Programs, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
Maki IkeuraDepartment of Brain Tumor, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
Michael DavidDivision of Biology, University of California San Diego, La Jolla, California.
Simon C WatkinsDepartment of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Saumendra N SarkarDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Cancer Virology Programs, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. saumen@pitt.edu OkadaH@neurosurg.ucsf.edu.
Hideho OkadaDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Department of Brain Tumor, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Department of Cancer Immunology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. saumen@pitt.edu OkadaH@neurosurg.ucsf.edu.
University of Pittsburgh · USUniversity of California San Diego · USUPMC Hillman Cancer Center · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0M
VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
Vector delivery to modify the brain tumor and its microenvironmentP01NS040923 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GLORIOSO, JOSEPH C · 2002 to 2012
$12.7M
Type-1 Antigen Presenting Cells in CNS Tumors - Key to Efficient Anti-Tumor T-CelP01CA132714 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KALINSKI, PAWEL · 2009 to 2013
$6.8M
Fluorescent Biosensors for Networks and PathwaysU54GM103529 · NIGMS · CARNEGIE-MELLON UNIVERSITY · PI WAGGONER, ALAN S. · 2012 to 2013
$6.3M
Novel Immunotherapy of Glioma using miR-17-92 Transfected T CellsR01NS055140 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI OKADA, HIDEHO · 2007 to 2015
$2.6M
Novel Modifiers of Toll-like and RIG-like Receptor SignalingU24AI082673 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SARKAR, SAUMENDRA N · 2009 to 2013
$1.5M
NCI NIH HHS P01 CA132714NCI NIH HHS P30 CA023100NCI NIH HHS P30 CA047904NCI NIH HHS P30CA047904NIAID NIH HHS 5U24AI082673NIAID NIH HHS U24 AI082673NIGMS NIH HHS U54 GM103529NINDS NIH HHS 2P01 NS40923NINDS NIH HHS 2R01 NS055140NINDS NIH HHS P01 NS040923NINDS NIH HHS R01 NS055140
6 · The paper itself

Abstract

Although type I IFNs play critical roles in antiviral and antitumor activity, it remains to be elucidated how type I IFNs are produced in sterile conditions of the tumor microenvironment and directly affect tumor-infiltrating immune cells. Mouse de novo gliomas show increased expression of type I IFN messages, and in mice, CD11b(+) brain-infiltrating leukocytes (BIL) are the main source of type I IFNs that are induced partially in a STING (stimulator of IFN genes)-dependent manner. Consequently, glioma-bearing Sting(Gt) (/Gt) mice showed shorter survival and lower expression levels of Ifns compared with wild-type mice. Furthermore, BILs of Sting(Gt) (/Gt) mice showed increased CD11b(+) Gr-1(+) immature myeloid suppressor and CD25(+) Foxp3(+) regulatory T cells (Treg) and decreased IFNγ-producing CD8(+) T cells. CD4(+) and CD8(+) T cells that received direct type I IFN signals showed lesser degrees of regulatory activity and increased levels of antitumor activity, respectively. Finally, intratumoral administration of a STING agonist (cyclic diguanylate monophosphate; c-di-GMP) improved the survival of glioma-bearing mice associated with enhanced type I IFN signaling, Cxcl10 and Ccl5, and T-cell migration into the brain. In combination with subcutaneous OVA peptide vaccination, c-di-GMP increased OVA-specific cytotoxicity of BILs and prolonged their survival. These data demonstrate significant contributions of STING to antitumor immunity via enhancement of type I IFN signaling in the tumor microenvironment and suggest a potential use of STING agonists for the development of effective immunotherapy, such as the combination with antigen-specific vaccinations.

Indexed as

Signal TransductionAnimalsCancer VaccinesCD11b AntigenCD11c AntigenCell Line, TumorCyclic GMPDisease Models, AnimalGene Expression ProfilingGliomaInterferon Type IMembrane ProteinsMiceMice, KnockoutSTING ProteinT-Lymphocyte Subsetsbis(3',5')-cyclic diguanylic acidCancer VaccinesCD11b AntigenCD11c AntigenCyclic GMPInterferon Type IMembrane ProteinsSting1 protein, mouseSTING Protein

Identifiers

PMID25300859
PMCPMC4258479
OpenAlexW2026830644

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.