Evidence map›Paper›PMID 21908444›Full record

ArticleNeuro-oncology2011

Thymus-derived rather than tumor-induced regulatory T cells predominate in brain tumors.

Derek A Wainwright, Sadhak Sengupta, Yu Han, Maciej S Lesniak

Open access · bronzeAbstract read
In one paragraph

Article in Neuro-oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

79 citing papers in PubMed, 121 citations in OpenAlex.

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19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Derek A WainwrightThe Brain Tumor Center, The University of Chicago, 5841 S. Maryland Ave, MC 3026, Chicago, IL 60637, USA.
Sadhak Sengupta
Yu Han
Maciej S Lesniak
University of Chicago · US

Funding

Regulatory T Cells in Malignant GliomaR01CA138587 · NCI · UNIVERSITY OF CHICAGO · PI LESNIAK, MACIEJ S · 2009 to 2013
$1.6M
The interaction of IDO and Tregs Leads to Immunosuppression in GliomaR00NS082381 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WAINWRIGHT, DEREK ALAN · 2014 to 2016
$735k
The interaction of IDO and Tregs Leads to Immunosuppression in GliomaK99NS082381 · NINDS · UNIVERSITY OF CHICAGO · PI WAINWRIGHT, DEREK ALAN · 2013 to 2014
$173k
The role of IDO and Th17 in an experimental mouse model of gliomaF32NS073366 · NINDS · UNIVERSITY OF CHICAGO · PI WAINWRIGHT, DEREK ALAN · 2011 to 2012
$86k
NCI NIH HHS R01 CA138587NCI NIH HHS R01CA138587NINDS NIH HHS F32 NS073366NINDS NIH HHS F32NS073366NINDS NIH HHS K99 NS082381NINDS NIH HHS R00 NS082381
6 · The paper itself

Abstract

Glioblastoma multiforme (GBM) is a highly malignant brain tumor with an average survival time of 15 months. Previously, we and others demonstrated that CD4(+)FoxP3(+) regulatory T cells (Tregs) infiltrate human GBM as well as mouse models that recapitulate malignant brain tumors. However, whether brain tumor-resident Tregs are thymus-derived natural Tregs (nTregs) or induced Tregs (iTregs), by the conversion of conventional CD4(+) T cells, has not been established. To investigate this question, we utilized the i.c. implanted GL261 cell-based orthotopic mouse model, the RasB8 transgenic astrocytoma mouse model, and a human GBM tissue microarray. We demonstrate that Tregs in brain tumors are predominantly thymus derived, since thymectomy, prior to i.c. GL261 cell implantation, significantly decreased the level of Tregs in mice with brain tumors. Accordingly, most Tregs in human GBM and mouse brain tumors expressed the nTreg transcription factor, Helios. Interestingly, a significant effect of the brain tumor microenvironment on Treg lineage programming was observed, based on higher levels of brain tumor-resident Tregs expressing glucocorticoid-induced tumor necrosis factor receptor and CD103 and lower levels of Tregs expressing CD62L and CD45RB compared with peripheral Tregs. Furthermore, there was a higher level of nTregs in brain tumors that expressed the proliferative marker Ki67 compared with iTregs and conventional CD4(+) T cells. Our study demonstrates that future Treg-depleting therapies should aim to selectively target systemic rather than intratumoral nTregs in brain tumor-specific immunotherapeutic strategies.

Indexed as

AnimalsBiomarkers, TumorBrain NeoplasmsDisease Models, AnimalFlow CytometryFluorescent Antibody TechniqueGene Expression ProfilingGlioblastomaHumansLymphocytes, Tumor-InfiltratingMiceMice, Inbred C57BLMice, TransgenicOligonucleotide Array Sequence AnalysisSurvival RateThymectomyBiomarkers, Tumor

Identifiers

PMID21908444
PMCPMC3223094
OpenAlexW2099314444

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.