Evidence map›Paper›PMID 31343989›Full record

ArticleThe Journal of clinical investigation2019

STING activation reprograms tumor vasculatures and synergizes with VEGFR2 blockade.

Hannah Yang, Won Suk Lee, So Jung Kong, Chang Gon Kim, Joo Hoon Kim, Sei Kyung Chang, Sewha Kim, Gwangil Kim, Hong Jae Chon, Chan Kim

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 193 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
193citing papers in PubMed, 1 pooled it
10.4field-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

193 citing papers in PubMed, 1 synthesis or guideline pooled it, 297 citations in OpenAlex.

  1. Bridging Radiotherapy to Immunotherapy: The IFN-JAK-STAT Axis.International journal of molecular sciences · 2021
    Pooled it
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133 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

10 authors at 2 institutions in 1 country.

Hannah YangMedical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
Won Suk LeeMedical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
So Jung KongMedical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
Chang Gon KimGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
Joo Hoon KimMedical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
Sei Kyung ChangDepartment of Radiation Oncology and.
Sewha KimDepartment of Pathology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
Gwangil KimDepartment of Pathology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
Hong Jae ChonMedical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
Chan KimMedical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
CHA University Bundang Medical Center · KRKorea Advanced Institute of Science and Technology · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The stimulator of interferon genes (STING) signaling pathway is a critical link between innate and adaptive immunity, and induces anti-tumor immune responses. STING is expressed in vasculatures, but its role in tumor angiogenesis has not been elucidated. Here we investigated STING-induced tumor vascular remodeling and the potential of STING-based combination immunotherapy. Endothelial STING expression was correlated with enhanced T-cell infiltration and prolonged survival in human colon and breast cancer. Intratumoral STING activation with STING agonists (cGAMP or RR-CDA) normalized tumor vasculatures in implanted and spontaneous cancers, but not in STING-deficient mice. These were mediated by upregulation of type I/II interferon genes and vascular stabilizing genes (e.g., Angpt1, Pdgfrb, and Col4a). STING in non-hematopoietic cells is as important as STING in hematopoietic cells to induce a maximal therapeutic efficacy of exogenous STING agonist. Vascular normalizing effects of STING agonists were dependent on type I interferon signaling and CD8+ T cells. Notably, STING-based immunotherapy was maximally effective when combined with VEGFR2 blockade and/or immune checkpoint blockade (αPD-1 or αCTLA-4), leading to complete regression of immunotherapy-resistant tumors. Our data show that intratumoral STING activation can normalize tumor vasculature and the tumor microenvironment, providing a rationale for combining STING-based immunotherapy and anti-angiogenic therapy.

Indexed as

AnimalsCD8-Positive T-LymphocytesImmunotherapyInterferon Type IMaleMembrane ProteinsMiceMice, TransgenicNeoplasm ProteinsNeoplasms, ExperimentalNeovascularization, PathologicNucleotides, CyclicSignal TransductionSTING ProteinTumor MicroenvironmentVascular Endothelial Growth Factor Receptor-2cyclic guanosine monophosphate-adenosine monophosphateInterferon Type IKdr protein, mouseMembrane ProteinsNeoplasm ProteinsNucleotides, CyclicSting1 protein, mouseSTING ProteinVascular Endothelial Growth Factor Receptor-2AngiogenesisCancerCancer immunotherapyendothelial cellsImmunology

Identifiers

PMID31343989
PMCPMC6763266
OpenAlexW2963305393

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.