Evidence map›Paper›PMID 37553183›Full record

ArticleJournal for immunotherapy of cancer2023

Functional tumor cell-intrinsic STING, not host STING, drives local and systemic antitumor immunity and therapy efficacy following cryoablation.

Mohammad Alshebremi, Suzanne L Tomchuck, Jay T Myers, Daniel T Kingsley, Saada Eid, Muta Abiff, Melissa Bonner, Shahrazad T Saab, Sung Hee Choi, Alex Yee-Chen Huang

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

10 citing papers in PubMed, 10 citations in OpenAlex.

  1. Trial
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  8. Journal for immunotherapy of cancer · 2025
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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

10 authors at 4 institutions in 2 countries.

Mohammad Alshebremi *Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Suzanne L Tomchuck *Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.ORCID 0000-0002-4068-3470
Jay T MyersDepartment of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Daniel T KingsleyDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.ORCID 0000-0002-5767-6509
Saada EidDepartment of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Muta AbiffDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Melissa BonnerDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.ORCID 0000-0001-5043-1907
Shahrazad T SaabDepartment of Pathology, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
Sung Hee ChoiDepartment of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Alex Yee-Chen HuangDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA alex.y.huang@case.edu.ORCID 0000-0002-5701-4521
University School · USQassim University · SARainbow Babies & Children's Hospital · USUniversity Hospitals of Cleveland · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
RESEARCH ONCOLOGY TRAINING GRANTT32CA059366 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI JACKSON, MARK W. · 1993 to 2025
$5.5M
NRSA Training CoreTL1TR002549 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI HARDING, CLIFFORD V · 2018 to 2022
$2.9M
Hamamatsu Nanozoomer S60 Digital Whole Slide ScannerS10OD024981 · OD · CASE WESTERN RESERVE UNIVERSITY · PI IMANISHI, YOSHIKAZU · 2018 to 2018
$303k
Role of IRF2BP2 in Tumor Immune EvasionF31CA254259 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI ABIFF, MUTA · 2021 to 2024
$209k
NCATS NIH HHS TL1 TR002549NCI NIH HHS F31 CA254259NCI NIH HHS T32 CA059366NIGMS NIH HHS T32 GM007250NIH HHS S10 OD024981
6 · The paper itself

Abstract

backgroundDespite its potential utility in delivering direct tumor killing and in situ whole-cell tumor vaccination, tumor cryoablation produces highly variable and unpredictable clinical response, limiting its clinical utility. The mechanism(s) driving cryoablation-induced local antitumor immunity and the associated abscopal effect is not well understood.

methodsThe aim of this study was to identify and explore a mechanism of action by which cryoablation enhances the therapeutic efficacy in metastatic tumor models. We used the subcutaneous mouse model of the rhabdomyosarcoma (RMS) cell lines RMS 76-9

resultsThe results show that cryoablation efficacy is dependent on both adaptive immunity and the STING signaling pathway. Contrary to current literature dictating an essential role of host-derived STING activation as a driver of antitumor immunity in vivo, we show that local tumor control, lung metastasis, and the abscopal effect on distant tumor are all critically dependent on a functioning tumor cell-intrinsic STING signaling pathway, which induces inflammatory chemokine and cytokine responses in the cryoablated TME. This reliance extends beyond cryoablation to include intratumoral STING agonist therapy. Additionally, surveys of gene expression databases and tissue microarrays of clinical tumor samples revealed a wide spectrum of expressions among STING-related signaling components.

conclusionsTumor cell-intrinsic STING pathway is a critical component underlying the effectiveness of cryoablation and suggests that expression of STING-related signaling components may serve as a potential therapy response biomarker. Our data also highlight an urgent need to further characterize tumor cell-intrinsic STING pathways and the associated downstream inflammatory response evoked by cryoablation and other STING-dependent therapy approaches.

Indexed as

CryosurgeryLung NeoplasmsAdaptive ImmunityAnimalsCytokinesMiceMice, Inbred C57BLTumor MicroenvironmentCytokinesAdaptive ImmunityImmunomodulationSarcomaTranslational Medical ResearchTumor Microenvironment

Identifiers

PMID37553183
PMCPMC10414127
OpenAlexW4385666785

What OpenQuestion holds

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LicenceCC BY-NC
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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.