Evidence map›Paper›PMID 35902861›Full record

ArticleJournal of translational medicine2022

Identification of genomic determinants contributing to cytokine release in immunotherapies and human diseases.

Lipei Shao, Alejandra Pelayo, Rongye Shi, Jinxia Ma, Hui Liu, Yihua Cai, Michaela Prochazkova, Robert P Somerville, Sandhya R Panch, Nirali N Shah and 2 more

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

Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 30% 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

5 citing papers in PubMed, 7 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.

Lipei Shao *Department of Transfusion Medicine, Center for Cellular Engineering, NIH Clinical Center, Bethesda, MD, 20892, USA.
Alejandra Pelayo *Department of Transfusion Medicine, Center for Cellular Engineering, NIH Clinical Center, Bethesda, MD, 20892, USA.
Rongye ShiDepartment of Transfusion Medicine, Center for Cellular Engineering, NIH Clinical Center, Bethesda, MD, 20892, USA.
Jinxia MaDepartment of Transfusion Medicine, Center for Cellular Engineering, NIH Clinical Center, Bethesda, MD, 20892, USA.
Hui LiuDepartment of Transfusion Medicine, Center for Cellular Engineering, NIH Clinical Center, Bethesda, MD, 20892, USA.
Yihua CaiDepartment of Transfusion Medicine, Center for Cellular Engineering, NIH Clinical Center, Bethesda, MD, 20892, USA.
Michaela ProchazkovaDepartment of Transfusion Medicine, Center for Cellular Engineering, NIH Clinical Center, Bethesda, MD, 20892, USA.
Robert P SomervilleDepartment of Transfusion Medicine, Center for Cellular Engineering, NIH Clinical Center, Bethesda, MD, 20892, USA.
Sandhya R PanchDepartment of Transfusion Medicine, Center for Cellular Engineering, NIH Clinical Center, Bethesda, MD, 20892, USA.
Nirali N ShahPediatric Oncology Branch, Center for Cancer Research, NIH NCI, Bethesda, MD, 20892, USA.
David F StroncekDepartment of Transfusion Medicine, Center for Cellular Engineering, NIH Clinical Center, Bethesda, MD, 20892, USA. DStroncek@cc.nih.gov.
Ping JinDepartment of Transfusion Medicine, Center for Cellular Engineering, NIH Clinical Center, Bethesda, MD, 20892, USA. PJin@cc.nih.gov.
National Institutes of Health Clinical Center · USCenter for Cancer Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCytokine release syndrome (CRS) is a strong immune system response that can occur as a result of the reaction of a cellular immunotherapy with malignant cells. While the frequency and management of CRS in CAR T-cell therapy has been well documented, there is emerging interest in pre-emptive treatment to reduce CRS severity and improve overall outcomes. Accordingly, identification of genomic determinants that contribute to cytokine release may lead to the development of targeted therapies to prevent or abrogate the severity of CRS.

methodsForty three clinical CD22 CAR T-cell products were collected for RNA extraction. 100 ng of mRNA was used for Nanostring assay analysis which is based on the nCounter platform. Several public datasets were used for validation purposes.

resultsWe found the expression of the PFKFB4 gene and glycolytic pathway activity were upregulated in CD22 CAR T-cells given to patients who developed CRS compared to those who did not experience CRS. Moreover, these results were further validated in cohorts with COVID-19, influenza infections and autoimmune diseases, and in tumor tissues. The findings were similar, except that glycolytic pathway activity was not increased in patients with influenza infections and systemic lupus erythematosus (SLE).

conclusionOur data strongly suggests that PFKFB4 acts as a driving factor in mediating cytokine release in vivo by regulating glycolytic activity. Our results suggest that it would beneficial to develop drugs targeting PFKFB4 and the glycolytic pathway for the treatment of CRS.

Indexed as

COVID-19Influenza, HumanCytokine Release SyndromeCytokinesGenomicsHumansImmunotherapyImmunotherapy, AdoptivePhosphofructokinase-2Receptors, Chimeric AntigenCytokinesPFKFB4 protein, humanPhosphofructokinase-2Receptors, Chimeric AntigenCAR T-cell therapyCytokine release syndromeGlycolysisPFKFB4

Identifiers

PMID35902861
PMCPMC9331024
OpenAlexW4288080584

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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.