Evidence map›Paper›PMID 26607445›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity.

Olivier Demaria, Aude De Gassart, Sanja Coso, Nicolas Gestermann, Jeremy Di Domizio, Lukas Flatz, Olivier Gaide, Olivier Michielin, Patrick Hwu, Tatiana V Petrova and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 355 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
355citing papers in PubMed, 1 pooled it
10.7field-weighted citation impact, top 1% 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

355 citing papers in PubMed, 1 synthesis or guideline pooled it, 569 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Therapeutic targeting of the cGAS-STING pathway in human disease.The Journal of clinical investigation · 2026
    Review
  10. Article
  11. Macrophage Extracellular Traps in Immunity and Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Nanovaccines with ferroptosis, necroptosis and STING-activation for synergistic immunotherapy.Journal of experimental & clinical cancer research : CR · 2026
    Article
  17. Review
  18. Article
  19. Article
  20. Review

295 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

14 authors at 5 institutions in 2 countries.

Olivier DemariaDepartment of Dermatology, University Hospital of Lausanne, 1011 Lausanne, Switzerland;
Aude De GassartDepartment of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland;
Sanja CosoDepartment of Oncology, University Hospital of Lausanne, 1011 Lausanne, Switzerland;
Nicolas GestermannDepartment of Dermatology, University Hospital of Lausanne, 1011 Lausanne, Switzerland;
Jeremy Di DomizioDepartment of Dermatology, University Hospital of Lausanne, 1011 Lausanne, Switzerland;
Lukas FlatzInstitute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland;
Olivier GaideDepartment of Dermatology, University Hospital of Lausanne, 1011 Lausanne, Switzerland;
Olivier MichielinDepartment of Oncology, University Hospital of Lausanne, 1011 Lausanne, Switzerland;
Patrick HwuDepartment of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030;
Tatiana V PetrovaDepartment of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland; Department of Oncology, University Hospital of Lausanne, 1011 Lausanne, Switzerland; Swiss Institute for Cancer Research, École polytechnique fédérale de Lausanne, 1015 Lausanne, Switzerland;
Fabio MartinonDepartment of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland;
Robert L ModlinDivision of Dermatology, and Departments of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095;
Daniel E SpeiserDepartment of Oncology, University Hospital of Lausanne, 1011 Lausanne, Switzerland; Ludwig Center for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland.
Michel GillietDepartment of Dermatology, University Hospital of Lausanne, 1011 Lausanne, Switzerland; michel.gilliet@chuv.ch.
University Hospital of Lausanne · CHUniversity of Lausanne · CHKantonsspital St. Gallen · CHThe University of Texas MD Anderson Cancer Center · USUniversity of California, Los Angeles · US

Funding

Molecular Mechanisms of pDC InteractionsP01CA128913 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HWU, PATRICK · 2008 to 2012
$9.3M
Vitamin D Metabolism in LeprosyP50AR063020 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MODLIN, ROBERT L · 2012 to 2016
$7.8M
Role of Vitamin D Prohormone 25-OHD in the Immune Response to TuberculosisR01HL119068 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LIU, PHILIP T., MODLIN, ROBERT L · 2014 to 2017
$1.5M
NCI NIH HHS P01 CA128913NHLBI NIH HHS R01 HL119068NIAMS NIH HHS P50 AR063020
6 · The paper itself

Abstract

Spontaneous CD8 T-cell responses occur in growing tumors but are usually poorly effective. Understanding the molecular and cellular mechanisms that drive these responses is of major interest as they could be exploited to generate a more efficacious antitumor immunity. As such, stimulator of IFN genes (STING), an adaptor molecule involved in cytosolic DNA sensing, is required for the induction of antitumor CD8 T responses in mouse models of cancer. Here, we find that enforced activation of STING by intratumoral injection of cyclic dinucleotide GMP-AMP (cGAMP), potently enhanced antitumor CD8 T responses leading to growth control of injected and contralateral tumors in mouse models of melanoma and colon cancer. The ability of cGAMP to trigger antitumor immunity was further enhanced by the blockade of both PD1 and CTLA4. The STING-dependent antitumor immunity, either induced spontaneously in growing tumors or induced by intratumoral cGAMP injection was dependent on type I IFNs produced in the tumor microenvironment. In response to cGAMP injection, both in the mouse melanoma model and an ex vivo model of cultured human melanoma explants, the principal source of type I IFN was not dendritic cells, but instead endothelial cells. Similarly, endothelial cells but not dendritic cells were found to be the principal source of spontaneously induced type I IFNs in growing tumors. These data identify an unexpected role of the tumor vasculature in the initiation of CD8 T-cell antitumor immunity and demonstrate that tumor endothelial cells can be targeted for immunotherapy of melanoma.

Indexed as

ImmunityAnimalsAntigens, NeoplasmCD8-Positive T-LymphocytesCell ProliferationCTLA-4 AntigenDendritic CellsDisease Models, AnimalDose-Response Relationship, ImmunologicEndothelial CellsInjections, IntralesionalInterferon Type ILymphocytes, Tumor-InfiltratingMelanomaMelanoma, ExperimentalMembrane ProteinsAntigens, NeoplasmCTLA-4 Antigencyclic guanosine monophosphate-adenosine monophosphateInterferon Type IMembrane ProteinsNucleotides, CyclicReceptor, Interferon alpha-betaSting1 protein, mouseSTING Proteinantitumor immunityCD8 T cellsSTINGtumor endothelial cellstype I IFNs

Identifiers

PMID26607445
PMCPMC4687570
OpenAlexW2173816666

What OpenQuestion holds

Textmetadata
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.