Evidence map›Paper›PMID 32004441›Full record

ArticleCancer cell2020

THEMIS-SHP1 Recruitment by 4-1BB Tunes LCK-Mediated Priming of Chimeric Antigen Receptor-Redirected T Cells.

Chuang Sun, Peishun Shou, Hongwei Du, Koichi Hirabayashi, Yuhui Chen, Laura E Herring, Sarah Ahn, Yang Xu, Kyogo Suzuki, Guangming Li and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed
8.0field-weighted citation impact, top 2% 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

106 citing papers in PubMed, 148 citations in OpenAlex.

  1. Article
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  4. Article
  5. Review
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  9. Article
  10. Article
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  13. Article
  14. Review
  15. CD4/CD8-p56Biomolecules · 2025
    Review
  16. Review
  17. Review
  18. Article
  19. Immunomodulatory Effects of Curcumin on CAR T-Cell Therapy.Antioxidants (Basel, Switzerland) · 2025
    Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Chuang SunLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Peishun ShouLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Hongwei DuLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Koichi HirabayashiLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Yuhui ChenLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Laura E HerringMichael Hooker Proteomics Center, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Sarah AhnLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Yang XuLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kyogo SuzukiLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Guangming LiLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Ourania TsahouridisLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Lishan SuLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Barbara SavoldoLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Gianpietro DottiLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: gdotti@med.unc.edu.
University of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Blocking type I interferon signaling to reverse T cell exhaustion and control HIV-1 reservoirsR01AI136990 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI AMARA, RAMA RAO, BOSINGER, STEVEN EDWARD · 2018 to 2022
$4.2M
Targeting the Ig-light chains with CAR-T cells in lymphoid tumorsR01CA193140 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DOTTI, GIANPIETRO · 2016 to 2020
$2.7M
NCI NIH HHS P30 CA016086NCI NIH HHS R01 CA193140NIAID NIH HHS R01 AI136990
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T cell costimulation mediated by CD28 and 4-1BB is essential for CAR-T cell-induced tumor regression. However, CD28 and 4-1BB differentially modulate kinetics, metabolism and persistence of CAR-T cells, and the mechanisms governing these differences are not fully understood. We found that LCK recruited into the synapse of CD28-encoding CAR by co-receptors causes antigen-independent CAR-CD3ζ phosphorylation and increased antigen-dependent T cell activation. In contrast, the synapse formed by 4-1BB-encoding CAR recruits the THEMIS-SHP1 phosphatase complex that attenuates CAR-CD3ζ phosphorylation. We further demonstrated that the CAR synapse can be engineered to recruit either LCK to enhance the kinetics of tumor killing of 4-1BB CAR-T cells or SHP1 to tune down cytokine release of CD28 CAR-T cells.

Indexed as

AnimalsCD28 AntigensCell Line, TumorCytokinesHumansIntercellular Signaling Peptides and ProteinsIntracellular Signaling Peptides and ProteinsLymphocyte ActivationMice, TransgenicProtein Tyrosine Phosphatase, Non-Receptor Type 6Receptors, Antigen, T-CellReceptors, Chimeric AntigenT-LymphocytesTumor Necrosis Factor Receptor Superfamily, Member 9CD28 AntigensCytokinesIntercellular Signaling Peptides and ProteinsIntracellular Signaling Peptides and ProteinsProtein Tyrosine Phosphatase, Non-Receptor Type 6Receptors, Antigen, T-CellReceptors, Chimeric Antigenthemis protein, mousethymocyte-expressed molecule involved in selection, humanTumor Necrosis Factor Receptor Superfamily, Member 94-1BBCAR-CD3ζCAR-TsCD28chimeric antigen receptorcytokine release syndrome (CRS)druggable engineeringkinasephosphatasephosphorylationsynapse

Identifiers

PMID32004441
PMCPMC7397569
OpenAlexW3003185702

What OpenQuestion holds

Textmetadata
LicenceTDM
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.