Evidence map›Paper›PMID 33452311›Full record

ArticleScientific reports2021

The anti-tumor effects of cetuximab in combination with VTX-2337 are T cell dependent.

Yinwen Cheng, Nicholas Borcherding, Ayomide Ogunsakin, Caitlin D Lemke-Miltner, Katherine N Gibson-Corley, Anand Rajan, Allen B Choi, Wattawan Wongpattaraworakul, Carlos H F Chan, Aliasger K Salem and 2 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 31% 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

9 citing papers in PubMed, 16 citations in OpenAlex.

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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

12 authors at 2 institutions in 1 country.

Yinwen ChengInterdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA, USA.
Nicholas BorcherdingDepartment of Pathology, University of Iowa, Iowa City, IA, USA.
Ayomide OgunsakinDepartment of Biochemistry, Lincoln University, Lincoln University, PA, USA.
Caitlin D Lemke-MiltnerHolden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
Katherine N Gibson-CorleyDepartment of Pathology, University of Iowa, Iowa City, IA, USA.
Anand RajanDepartment of Pathology, University of Iowa, Iowa City, IA, USA.
Allen B ChoiDepartment of Pathology, University of Iowa, Iowa City, IA, USA.
Wattawan WongpattaraworakulDepartment of Pathology, University of Iowa, Iowa City, IA, USA.
Carlos H F ChanHolden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
Aliasger K SalemInterdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA, USA.
George J WeinerHolden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
Andrean L SimonsInterdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA, USA. andrean-simons@uiowa.edu.
University of Iowa · USLincoln University - Pennsylvania · US

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Douglas Robert Spitz · 2000 to 2026
$70.0M
Pulmonary Toxicology Facility CoreP30ES005605 · NIEHS · UNIVERSITY OF IOWA · PI Brandi Janssen · 1990 to 2026
$40.5M
Role of inflammation in resistance to EGFR inhibitors in head and neck cancerR01DE024550 · NIDCR · UNIVERSITY OF IOWA · PI BURNETT, ANDREAN LLEWELA · 2014 to 2018
$2.0M
NIDCR NIH HHS R01 DE024550NIEHS NIH HHS P30 ES005605
6 · The paper itself

Abstract

The Toll-like receptor 8 (TLR8) agonist VTX-2337 (motolimod) is an anti-cancer immunotherapeutic agent that is believed to augment natural killer (NK) and dendritic cell (DC) activity. The goal of this work is to examine the role of TLR8 expression/activity in head and neck squamous cell carcinoma (HNSCC) to facilitate the prediction of responders to VTX-2337-based therapy. The prognostic role of TLR8 expression in HNSCC patients was assessed by TCGA and tissue microarray analyses. The anti-tumor effect of VTX-2337 was determined in SCCVII/C3H, mEERL/C57Bl/6 and TUBO-human EGFR/BALB/c syngeneic mouse models. The effect of combined VTX-2337 and cetuximab treatment on tumor growth, survival and immune cell recruitment was assessed. TLR8 expression was associated with CD8+ T cell infiltration and favorable survival outcomes. VTX-2337 delayed tumor growth in all 3 syngeneic mouse models and significantly increased the survival of cetuximab-treated mice. The anti-tumor effects of VTX-2337+ cetuximab were accompanied by increased splenic lymphoid DCs and IFNγ+ CD4+ and tumor-specific CD8+ T cells. Depletion of CD4+ T cells, CD8+ T cells and NK cells were all able to abolish the anti-tumor effect of VTX-2337+ cetuximab. Altogether, VTX-2337 remains promising as an adjuvant for cetuximab-based therapy however patients with high TLR8 expression may be more likely to derive benefit from this drug combination compared to patients with low TLR8 expression.

Indexed as

AnimalsAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsBenzazepinesBiomarkers, PharmacologicalCD8-Positive T-LymphocytesCell Line, TumorCetuximabCytokinesDatabases, GeneticFemaleGene ExpressionGene Expression Regulation, NeoplasticHumansKiller Cells, NaturalMaleAntineoplastic AgentsBenzazepinesBiomarkers, PharmacologicalCetuximabCytokinesTLR8 protein, humanToll-Like Receptor 8VTX-2337

Identifiers

PMID33452311
PMCPMC7810827
OpenAlexW3123520015

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.