Evidence map›Paper›PMID 32169869›Full record

ArticleJournal for immunotherapy of cancer2020

Potent STING activation stimulates immunogenic cell death to enhance antitumor immunity in neuroblastoma.

Lihong Wang-Bishop, Mohamed Wehbe, Daniel Shae, Jamaal James, Benjamin C Hacker, Kyle Garland, Plamen P Chistov, Marjan Rafat, Justin M Balko, John T Wilson

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed
7.9field-weighted citation impact, top 2% 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

111 citing papers in PubMed, 163 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. PPT1 is a negative regulator of STING signaling in cancer cells and its inhibition reactivates immune surveillance in cold tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  20. Review

51 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.

Lihong Wang-BishopDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Mohamed WehbeDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Daniel ShaeDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Jamaal JamesDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Benjamin C HackerDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Kyle GarlandDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Plamen P ChistovDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Marjan RafatDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, USA.ORCID 0000-0002-9444-4379
Justin M BalkoDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
John T WilsonDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, USA john.t.wilson@vanderbilt.edu.ORCID 0000-0002-9144-2634
Vanderbilt University · USVanderbilt University Medical Center · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Deconstructing the Tumor Microenvironment and its Role in MetastasisR00CA201304 · NCI · VANDERBILT UNIVERSITY · PI RAFAT, MARJAN · 2018 to 2020
$728k
NCI NIH HHS P30 CA068485NCI NIH HHS R00 CA201304NIDDK NIH HHS P30 DK058404
6 · The paper itself

Abstract

backgroundNeuroblastoma (NB) is a childhood cancer for which new treatment options are needed. The success of immune checkpoint blockade in the treatment of adult solid tumors has prompted the exploration of immunotherapy in NB; however, clinical evidence indicates that the vast majority of NB patients do not respond to single-agent checkpoint inhibitors. This motivates a need for therapeutic strategies to increase NB tumor immunogenicity. The goal of this study was to evaluate a new immunotherapeutic strategy for NB based on potent activation of the stimulator of interferon genes (STING) pathway.

methodsTo promote STING activation in NB cells and tumors, we utilized STING-activating nanoparticles (STING-NPs) that are designed to mediate efficient cytosolic delivery of the endogenous STING ligand, 2'3'-cGAMP. We investigated tumor-intrinsic responses to STING activation in both MYCN-amplified and non-amplified NB cell lines, evaluating effects on STING signaling, apoptosis, and the induction of immunogenic cell death. The effects of intratumoral administration of STING-NPs on CD8

resultsThe efficient cytosolic delivery of 2'3'-cGAMP enabled by STING-NPs triggered tumor-intrinsic STING signaling effects in both MYCN-amplified and non-amplified NB cell lines, resulting in increased expression of interferon-stimulated genes and pro-inflammatory cytokines as well as NB cell death at concentrations 2000-fold to 10000-fold lower than free 2'3'-cGAMP. STING-mediated cell death in NB was associated with release or expression of several danger associated molecular patterns that are hallmarks of immunogenic cell death, which was further validated via cell-based vaccination and tumor challenge studies. Intratumoral administration of STING-NPs enhanced STING activation relative to free 2'3'-cGAMP in NB tumor models, converting poorly immunogenic tumors into tumoricidal and T cell-inflamed microenvironments and resulting in inhibition of tumor growth, increased survival, and induction of immunological memory that protected against tumor re-challenge. In a model of MYCN-amplified NB, STING-NPs generated an abscopal response that inhibited distal tumor growth and improved response to PD-L1 immune checkpoint blockade.

conclusionsWe have demonstrated that activation of the STING pathway, here enabled by a nanomedicine approach, stimulates immunogenic cell death and remodels the tumor immune microenvironment to inhibit NB tumor growth and improve responses to immune checkpoint blockade, providing a multifaceted immunotherapeutic approach with potential to enhance immunotherapy outcomes in NB.

Indexed as

HumansImmunogenic Cell DeathImmunotherapyMembrane ProteinsNeuroblastomaSignal TransductionSTING ProteinMembrane ProteinsSTING1 protein, humanSTING Proteinimmunologytumours

Identifiers

PMID32169869
PMCPMC7069313
OpenAlexW3011282656

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.