Evidence map›Paper›PMID 39658572›Full record

ArticleNature communications2024

Cullin-5 deficiency promotes chimeric antigen receptor T cell effector functions potentially via the modulation of JAK/STAT signaling pathway.

Yoshitaka Adachi, Seitaro Terakura, Masahide Osaki, Yusuke Okuno, Yoshitaka Sato, Ken Sagou, Yuki Takeuchi, Hirofumi Yokota, Kanae Imai, Peter Steinberger and 4 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
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

15 citing papers in PubMed.

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  14. The mFrontiers in oncology · 2025
    Article
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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

14 authors.

Yoshitaka AdachiDepartment of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. yadachi@umich.edu.ORCID 0000-0002-9763-5533
Seitaro TerakuraDepartment of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. tseit@med.nagoya-u.ac.jp.ORCID 0000-0002-1194-8046
Masahide OsakiDepartment of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yusuke OkunoDepartment of Virology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.ORCID 0000-0003-3139-9272
Yoshitaka SatoDepartment of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID 0000-0002-8541-6413
Ken SagouDepartment of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yuki TakeuchiDepartment of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hirofumi YokotaDepartment of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID 0009-0005-8979-5181
Kanae ImaiDepartment of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Peter SteinbergerDivision for Immune Receptors and T Cell Activation, Institute of Immunology, Medical University of Vienna, Vienna, Austria.ORCID 0000-0001-6848-4097
Judith LeitnerDivision for Immune Receptors and T Cell Activation, Institute of Immunology, Medical University of Vienna, Vienna, Austria.ORCID 0000-0002-7156-1759
Ryo HanajiriDepartment of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Makoto MurataDepartment of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID 0000-0001-5488-4364
Hitoshi KiyoiDepartment of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID 0000-0001-6382-9498

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T cell is a promising therapy for cancer, but factors that enhance the efficacy of CAR T cell remain elusive. Here we perform a genome-wide CRISPR screening to probe genes that regulate the proliferation and survival of CAR T cells following repetitive antigen stimulations. We find that genetic ablation of CUL5, encoding a core element of the multi-protein E3 ubiquitin-protein ligase complex, cullin-RING ligase 5, enhances human CD19 CAR T cell expansion potential and effector functions, potentially via the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. In this regard, CUL5 knockout CD19 CAR T cells show sustained STAT3 and STAT5 phosphorylation, as well as delayed phosphorylation and degradation of JAK1 and JAK3. In vivo, shRNA-mediated knockdown of CUL5 enhances CD19 CAR T treatment outcomes in tumor-bearing mice. Our findings thus imply that targeting CUL5 in the ubiquitin system may enhance CAR T cell effector functions to enhance immunotherapy efficacy.

Indexed as

Cullin ProteinsReceptors, Chimeric AntigenSignal TransductionT-LymphocytesAnimalsAntigens, CD19Cell Line, TumorCell ProliferationCRISPR-Cas SystemsHumansImmunotherapy, AdoptiveJanus KinasesMicePhosphorylationSTAT3 Transcription FactorSTAT5 Transcription FactorAntigens, CD19CUL5 protein, humanCullin ProteinsJanus KinasesReceptors, Chimeric AntigenSTAT3 Transcription FactorSTAT5 Transcription FactorSTAT Transcription Factors

Identifiers

PMID39658572
PMCPMC11631977

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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.