Evidence map›Paper›PMID 32642723›Full record

ArticleNeuro-oncology advances

Downregulation of PD-L1 via FKBP5 by celecoxib augments antitumor effects of PD-1 blockade in a malignant glioma model.

Izumi Yamaguchi, Kohei Nakajima, Kenji Shono, Yoshifumi Mizobuchi, Toshitaka Fujihara, Eiji Shikata, Tadashi Yamaguchi, Keiko Kitazato, Oltea Sampetrean, Hideyuki Saya and 1 more

Open access · goldAbstract read
In one paragraph

Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.0field-weighted citation impact, top 21% 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

16 citing papers in PubMed, 18 citations in OpenAlex.

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  8. Cancer resistance via the downregulation of the tumor suppressorsExploration of targeted anti-tumor therapy · 2023
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  13. EMP3 mediates glioblastoma-associated macrophage infiltration to drive T cell exclusion.Journal of experimental & clinical cancer research : CR · 2021
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  16. DNA Methylation ofCancers · 2020
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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

11 authors at 2 institutions in 1 country.

Izumi YamaguchiDepartment of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Kohei NakajimaDepartment of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Kenji ShonoDepartment of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Yoshifumi MizobuchiDepartment of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Toshitaka FujiharaDepartment of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Eiji ShikataDepartment of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Tadashi YamaguchiDepartment of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Keiko KitazatoDepartment of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Oltea SampetreanDivision of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
Hideyuki SayaDivision of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
Yasushi TakagiDepartment of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Tokushima University · JPKeio University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAntitumor therapies targeting programmed cell death-1 (PD-1) or its ligand-1 (PD-L1) are used in various cancers. However, in glioblastoma (GBM), the expression of PD-L1 varies between patients, and the relationship between this variation and the efficacy of anti-PD-1 antibody therapy remains unclear. High expression levels of PD-L1 affect the proliferation and invasiveness of GBM cells. As COX-2 modulates PD-L1 expression in cancer cells, we tested the hypothesis that the COX-2 inhibitor celecoxib potentiates anti-PD-1 antibody treatment via the downregulation of PD-L1.

methodsSix-week-old male C57BL/6 mice injected with murine glioma stem cells (GSCs) were randomly divided into four groups treated with vehicle, celecoxib, anti-PD-1 antibody, or celecoxib plus anti-PD-1 antibody and the antitumor effects of these treatments were assessed. To verify the mechanisms underlying these effects, murine GSCs and human GBM cells were studied in vitro.

resultsCompared with that with each single treatment, the combination of celecoxib and anti-PD-1 antibody treatment significantly decreased tumor volume and prolonged survival. The high expression of PD-L1 was decreased by celecoxib in the glioma model injected with murine GSCs, cultured murine GSCs, and cultured human GBM cells. This reduction was associated with post-transcriptional regulation of the co-chaperone FK506-binding protein 5 (FKBP5).

conclusionsCombination therapy with anti-PD-1 antibody plus celecoxib might be a promising therapeutic strategy to target PD-L1 in glioblastoma. The downregulation of highly-expressed PD-L1 via FKBP5, induced by celecoxib, could play a role in its antitumor effects.

Indexed as

celecoxibFKBP5glioblastomaPD-1PD-L1

Identifiers

PMID32642723
PMCPMC7212915
OpenAlexW2997623347

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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.