Evidence map›Paper›PMID 30840664›Full record

ArticlePloS one2019

Ex vivo-expanded highly purified natural killer cells in combination with temozolomide induce antitumor effects in human glioblastoma cells in vitro.

Yoshitaka Tanaka, Tsutomu Nakazawa, Mitsutoshi Nakamura, Fumihiko Nishimura, Ryosuke Matsuda, Koji Omoto, Yoichi Shida, Toshiharu Murakami, Ichiro Nakagawa, Yasushi Motoyama and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

29 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Advances in NK cell therapy for brain tumors.NPJ precision oncology · 2023
    Review
  15. Natural Killer Cell-Based Immunotherapy against Glioblastoma.International journal of molecular sciences · 2023
    Review
  16. Review
  17. Review
  18. Article
  19. Advances in NK cell production.Cellular & molecular immunology · 2022
    Review
  20. 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

13 authors at 2 institutions in 1 country.

Yoshitaka TanakaDepartment of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan.ORCID 0000-0001-9824-9653
Tsutomu NakazawaDepartment of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan.ORCID 0000-0003-4286-9356
Mitsutoshi NakamuraDepartment of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan.
Fumihiko NishimuraDepartment of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan.
Ryosuke MatsudaDepartment of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan.
Koji OmotoDepartment of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan.ORCID 0000-0002-3132-912X
Yoichi ShidaDepartment of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan.
Toshiharu MurakamiDepartment of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan.
Ichiro NakagawaDepartment of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan.
Yasushi MotoyamaDepartment of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan.
Hiromichi MoritaGrandsoul Research Institute for Immunology, Inc., Uda, Nara, Japan.
Takahiro TsujimuraClinic Grandsoul Nara, Uda, Nara, Japan.
Hiroyuki NakaseDepartment of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan.
Nara Medical University · JPNara City Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma is the leading malignant glioma with a poor prognosis. This study aimed to investigate the antitumor effects of natural killer cells in combination with temozolomide as the standard chemotherapeutic agent for glioblastoma. Using a simple, feeder-less, and chemically defined culture method, we expanded human peripheral blood mononuclear cells and assessed the receptor expression, natural killer cell activity, and regulatory T cell frequency in expanded cells. Next, using the standard human glioblastoma cell lines (temozolomide-sensitive U87MG, temozolomide-resistant T98G, and LN-18), we assessed the ligand expressions of receptors on natural killer cells. Furthermore, the antitumor effects of the combination of the expanded natural killer cells and temozolomide were assessed using growth inhibition assays, apoptosis detection assays, and senescence-associated β-galactosidase activity assays in the glioblastoma cell lines. Novel culture systems were sufficient to attain highly purified (>98%), expanded (>440-fold) CD3-/CD56+ peripheral blood-derived natural killer cells. We designated the expanded population as genuine induced natural killer cells. Genuine induced natural killer cells exhibited a high natural killer activity and low regulatory T cell frequency compared with lymphokine-activated killer cells. Growth inhibition assays revealed that genuine induced natural killer cells inhibited the glioblastoma cell line growth but enhanced temozolomide-induced inhibition effects in U87MG. Apoptosis detection assays revealed that genuine induced natural killer cells induced apoptosis in the glioblastoma cell lines. Furthermore, senescence-associated β-galactosidase activity assays revealed that temozolomide induced senescence in U87MG. Genuine induced natural killer cells induce apoptosis in temozolomide-sensitive and temozolomide-resistant glioblastoma cells and enhances temozolomide-induced antitumor effects in different mechanisms. Hence, the combination of genuine induced natural killer cells and temozolomide may prove to be a promising immunochemotherapeutic approach in patients with glioblastoma if the antitumor effects in vivo can be demonstrated.

Indexed as

ApoptosisCoculture TechniquesGlioblastomaHumansImmunity, CellularK562 CellsKiller Cells, NaturalTemozolomideTemozolomide

Identifiers

PMID30840664
PMCPMC6402639
OpenAlexW2921252083

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.