Evidence map›Paper›PMID 31052261›Full record

ArticleCancers2019

Hypoxia Selectively Impairs CAR-T Cells In Vitro.

Robert Berahovich, Xianghong Liu, Hua Zhou, Elias Tsadik, Shirley Xu, Vita Golubovskaya, Lijun Wu

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 4% 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

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.

  1. Pooled it
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  14. Article
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  16. Prospects of Synergy: Local Interventions and CAR T Cell Therapy in Solid Tumors.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
  17. Article
  18. Review
  19. Article
  20. Engineering metabolism to modulate immunity.Advanced drug delivery reviews · 2024
    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

7 authors at 2 institutions in 1 country.

Robert BerahovichProMab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA. robert.berahovich@promab.com.
Xianghong LiuProMab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA. Xianghong.liu@promab.com.
Hua ZhouProMab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA. hua.zhou@promab.com.
Elias TsadikProMab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA. elias.tsadik@promab.com.
Shirley XuProMab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA. shirley.xu@promab.com.
Vita GolubovskayaProMab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA. vita.gol@promab.com.
Lijun WuProMab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA. john@promab.com.
Promega (United States) · USUniversity of Oklahoma Health Sciences Center · US

Funding

Science and Technology Department, China 2016SK2071
6 · The paper itself

Abstract

Hypoxia is a major characteristic of the solid tumor microenvironment. To understand how chimeric antigen receptor-T cells (CAR-T cells) function in hypoxic conditions, we characterized CD19-specific and BCMA-specific human CAR-T cells generated in atmospheric (18% oxygen) and hypoxic (1% oxygen) culture for expansion, differentiation status, and CD4:CD8 ratio. CAR-T cells expanded to a much lower extent in 1% oxygen than in 18% oxygen. Hypoxic CAR-T cells also had a less differentiated phenotype and a higher CD4:CD8 ratio than atmospheric CAR-T cells. CAR-T cells were then added to antigen-positive and antigen-negative tumor cell lines at the same or lower oxygen level and characterized for cytotoxicity, cytokine and granzyme B secretion, and PD-1 upregulation. Atmospheric and hypoxic CAR-T cells exhibited comparable cytolytic activity and PD-1 upregulation; however, cytokine production and granzyme B release were greatly decreased in 1% oxygen, even when the CAR-T cells were generated in atmospheric culture. Together, these data show that at solid tumor oxygen levels, CAR-T cells are impaired in expansion, differentiation and cytokine production. These effects may contribute to the inability of CAR-T cells to eradicate solid tumors seen in many patients.

Indexed as

BCMACAR-TCD19hypoxiaimmunotherapymicroenvironmenttumor

Identifiers

PMID31052261
PMCPMC6562712
OpenAlexW2943291219

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.