Evidence map›Paper›PMID 23804077›Full record

ArticleGene therapy2013

Downregulation of Stat3 in melanoma: reprogramming the immune microenvironment as an anticancer therapeutic strategy.

P U Emeagi, S Maenhout, N Dang, C Heirman, K Thielemans, K Breckpot

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

18 citing papers in PubMed, 37 citations in OpenAlex.

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  11. The Journey ofFrontiers in immunology · 2018
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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

6 authors at 1 institution in 1 country.

P U EmeagiLaboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Jette, Belgium.
S Maenhout
N Dang
C Heirman
K Thielemans
K Breckpot
Vrije Universiteit Brussel · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Persistent activation of the transcription factor, signal transducer and activator of transcription 3 (Stat3) has been shown to mediate several oncogenic features in many types of cancers, including melanoma. In this study, we investigated whether lentiviral (LV) delivery of Stat3-targeting short hairpin RNA (shRNA; LV-shStat3) to K1735-C4 melanoma cells modulates antitumor immunity. Three shStat3 sequences, starting at the position 446, 830 and 1412, were cloned into a mir30 cassette. A shRNA with scrambled sequence served as a control. Transduction with LV-shStat3 resulted in downregulation of Stat3 in vitro. The latter coincided with low cell viability, a reduced expression of survivin and matrix metalloproteinase (MMP)-2. A single injection of LV-shStat3 in K1735-C4 tumors efficiently downregulated Stat3 in vivo and resulted in reduction of both vascular endothelial growth factor secretion and in myeloid-derived suppressor cell (MDSC) numbers. In contrast, we observed an increase in interleukin-6 and interferon-γ secretion, mature dendritic cells (DCs) and CD8(+) T cells. Both DCs and CD8(+) T cells displayed enhanced activity, whereas granulocytic MDSCs lost their suppressive capacity upon Stat3 downregulation. Importantly, a single injection of LV-shStat3 was sufficient to reduce tumor growth, hence prolong survival of tumor-bearing mice. These data demonstrate that Stat3 downregulation in melanoma reinvigorates existing antitumor immunity.

Indexed as

AnimalsCell Line, TumorCell SurvivalDown-RegulationFemaleGene Expression Regulation, NeoplasticGenetic VectorsHEK293 CellsHumansInhibitor of Apoptosis ProteinsLentivirusMatrix Metalloproteinase 2MelanomaMelanoma, ExperimentalMiceMice, Inbred C57BLBirc5 protein, mouseInhibitor of Apoptosis ProteinsMatrix Metalloproteinase 2Repressor ProteinsRNA, Small InterferingSTAT3 Transcription FactorSurvivin

Identifiers

PMID23804077
OpenAlexW2078917646

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.