Evidence map›Paper›PMID 32516591›Full record

ArticleCancer cell2020

Multi-phenotype CRISPR-Cas9 Screen Identifies p38 Kinase as a Target for Adoptive Immunotherapies.

Devikala Gurusamy, Amanda N Henning, Tori N Yamamoto, Zhiya Yu, Nikolaos Zacharakis, Sri Krishna, Rigel J Kishton, Suman K Vodnala, Arash Eidizadeh, Li Jia and 8 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 100 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed, 2 pooled it
7.9field-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

100 citing papers in PubMed, 2 syntheses or guidelines pooled it, 153 citations in OpenAlex.

  1. Pooled it
  2. Efficacy ofFrontiers in pharmacology · 2024
    Pooled it
  3. Trial
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 4 institutions in 1 country.

Devikala GurusamySurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA. Electronic address: gurusamyd@mail.nih.gov.
Amanda N HenningSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Tori N YamamotoSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
Zhiya YuSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Nikolaos ZacharakisSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Sri KrishnaSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Rigel J KishtonSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Suman K VodnalaSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Arash EidizadehSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Li JiaSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Christine M KariyaSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Mary A BlackSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Robert EilSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Douglas C PalmerSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Jenny H PanSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Madhusudhanan SukumarSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Shashank J PatelSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA. Electronic address: shashank.oxin@gmail.com.
Nicholas P RestifoSurgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: restifon@mail.nih.gov.
National Cancer Institute · USNational Institutes of Health · USCenter for Cancer Research · USUniversity of Pennsylvania · US

Funding

Center for Cell-based Therapy - CuresZIABC011855 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GRETEN, TIM · 2020 to 2025
$6.5M
Building on the success of the adoptive immunotherapy of cancerZ01BC010763 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI RESTIFO, NICHOLAS P · 2006 to 2008
$6.4M
Intramural NIH HHS Z01 BC010763Intramural NIH HHS ZIA BC011855
6 · The paper itself

Abstract

T cells are central to all currently effective cancer immunotherapies, but the characteristics defining therapeutically effective anti-tumor T cells have not been comprehensively elucidated. Here, we delineate four phenotypic qualities of effective anti-tumor T cells: cell expansion, differentiation, oxidative stress, and genomic stress. Using a CRISPR-Cas9-based genetic screen of primary T cells we measured the multi-phenotypic impact of disrupting 25 T cell receptor-driven kinases. We identified p38 kinase as a central regulator of all four phenotypes and uncovered transcriptional and antioxidant pathways regulated by p38 in T cells. Pharmacological inhibition of p38 improved the efficacy of mouse anti-tumor T cells and enhanced the functionalities of human tumor-reactive and gene-engineered T cells, paving the way for clinically relevant interventions.

Indexed as

CRISPR-Cas SystemsPhenotypeAnimalsBreast NeoplasmsCell DifferentiationFemaleGenetic EngineeringImmunotherapy, AdoptiveMaleMelanoma, ExperimentalMiceMice, Inbred C57BLMice, Knockoutp38 Mitogen-Activated Protein KinasesReceptors, Antigen, T-CellT-Lymphocytesp38 Mitogen-Activated Protein KinasesReceptors, Antigen, T-Celladoptive transfer immunotherapyCD19 CAR T cellCRISPR-Cas9 screendifferentiationDNA damagemulti-phenotypeneoantigen TILNY-ESO-1p38ROS

Identifiers

PMID32516591
PMCPMC10323690
OpenAlexW3033006672

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.