Evidence map›Paper›PMID 31350431›Full record

ArticleScientific reports2019

A mathematical model of combined CD8 T cell costimulation by 4-1BB (CD137) and OX40 (CD134) receptors.

Anna Konstorum, Anthony T Vella, Adam J Adler, Reinhard C Laubenbacher

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

6 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Recent advances in CAR-T cell engineering.Journal of hematology & oncology · 2020
    Review
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

4 authors at 2 institutions in 1 country.

Anna KonstorumCenter for Quantitative Medicine, School of Medicine, UConn Health, 263 Farmington Ave., Farmington, CT, USA. konstorum@uchc.edu.ORCID http://orcid.org/0000-0003-4024-2058
Anthony T VellaDepartment of Immunology, School of Medicine, UConn Health, 263 Farmington Ave., Farmington, CT, USA.
Adam J AdlerDepartment of Immunology, School of Medicine, UConn Health, 263 Farmington Ave., Farmington, CT, USA.
Reinhard C LaubenbacherCenter for Quantitative Medicine, School of Medicine, UConn Health, 263 Farmington Ave., Farmington, CT, USA.
UConn Health · USJackson Laboratory · US

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI Paul Robson · 1985 to 2026
$61.9M
Breaking Tolerance to Induce Tumor-Specific Cytotoxic CD4 Th1 CellsR01AI094640 · NIAID · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI ADLER, ADAM J, VELLA, ANTHONY T · 2012 to 2016
$1.9M
Test if antitumor T cells use a putative super-enhancer in the Il1rl2-Il1rl1 intergenic region to form "innate-like" responses to cytokinesR21AI139891 · NIAID · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI ADLER, ADAM J, VELLA, ANTHONY T · 2018 to 2019
$439k
Multiscale modeling of synergistic T cell activation for cancer immunotherapyF32CA214030 · NCI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI KONSTORUM, ANNA · 2017 to 2018
$116k
NCI NIH HHS F32 CA214030NCI NIH HHS P30 CA034196NIAID NIH HHS R01 AI094640NIAID NIH HHS R21 AI139891
6 · The paper itself

Abstract

Combined agonist stimulation of the TNFR costimulatory receptors 4-1BB (CD137) and OX40(CD134) has been shown to generate supereffector CD8 T cells that clonally expand to greater levels, survive longer, and produce a greater quantity of cytokines compared to T cells stimulated with an agonist of either costimulatory receptor individually. In order to understand the mechanisms for this effect, we have created a mathematical model for the activation of the CD8 T cell intracellular signaling network by mono- or dual-costimulation. We show that supereffector status is generated via downstream interacting pathways that are activated upon engagement of both receptors, and in silico simulations of the model are supported by published experimental results. The model can thus be used to identify critical molecular targets of T cell dual-costimulation in the context of cancer immunotherapy.

Indexed as

Lymphocyte ActivationModels, TheoreticalAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCytokinesHumansImmunotherapyNeoplasmsPhenotypeReceptors, Antigen, T-CellReceptors, OX40Signal TransductionTumor Necrosis Factor Receptor Superfamily, Member 9CytokinesReceptors, Antigen, T-CellReceptors, OX40Tumor Necrosis Factor Receptor Superfamily, Member 9

Identifiers

PMID31350431
PMCPMC6659676
OpenAlexW2965048805

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.