Evidence map›Paper›PMID 34098947›Full record

ArticleCancer cell international2021

Overcoming the UCB HSCs -Derived NK cells Dysfunction through Harnessing RAS/MAPK, IGF-1R and TGF-β Signaling Pathways.

Alireza Shokouhifar, Gholamreza Anani Sarab, Mahboubeh Yazdanifar, Mohammad Fereidouni, Masoumeh Nouri, Marzieh Ebrahimi

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

Article in Cancer cell international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

13 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. NK cells in HPV-related tumorigenesis: mechanisms and clinical applications.Frontiers in cellular and infection microbiology · 2025
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Stem Cell Therapy and Innate Lymphoid Cells.Stem cells international · 2022
    Review
  12. Review
  13. Article
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

6 authors at 4 institutions in 2 countries.

Alireza ShokouhifarDepartment of Molecular Medicine, Genomic Research Center, Birjand University of Medical Sciences, Birjand, Iran.
Gholamreza Anani SarabCellular & Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran. ghansa@yahoo.co.
Mahboubeh YazdanifarStem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.
Mohammad FereidouniCellular & Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.
Masoumeh NouriR&D Department, Royan Stem Cell Technology Co, Tehran, Iran.
Marzieh EbrahimiStem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA. mebrahimi@royaninstitute.org.ORCID http://orcid.org/0000-0003-1140-0379
Birjand University of Medical Sciences · IRCalifornia Institute for Regenerative Medicine · USRoyan Institute · IRStanford University · US

Funding

Birjand University of Medical Sciences 455421cancer research center of cancer institute of Iran (Shams cancer charity) 37312-202-01-97Royan Stem Cell Technology Co. RSCT96030201
6 · The paper itself

Abstract

backgroundThe natural killer (NK) cells differentiated from umbilical cord blood (UCB) hematopoietic stem cells (HSCs) may be more suitable for cell-based immunotherapy compared to the NK cells from adult donors. This is due to the possibility to choose alloreactive donors and potentially more robust in vivo expansion. However, the cytotoxicity of UCB-HSC-derived NK cells against cancer cells might be suboptimal. To overcome this obstacle, we attempted to generate NK cells with potent antitumor activity by targeting RAS/MAPK, IGF-1R and TGF-β signaling pathways using IL-15, IGF-1 and SIS3 respectively.

methodsThe CD34 + cells were isolated from human UCB mononuclear cells through magnetic activation cell sorting (MACS) with purity of (≥ 90%) and were subjected to differentiate into NK cells. After 21 days of induction with SFTG36 (SCF, FLt-3L, TPO, GM-CSF, IL-3 and IL-6), IS721 (IGF-1, SIS3, IL-7 and IL-21) and IL-15/Hsp70 media, NK cells phenotypes were studied and their cytotoxicity against K562 human erythroleukemia cells and SKOV3 ovarian carcinoma cells was analyzed.

resultsThe NK cells induced in SFTG36/IS721 medium were selected for activation due to their higher expression of CD56 + 16 + CD3 -  (93.23% ± 0.75) and mean fluorescence intensity (MFI) of NKG2D + (168.66 ± 20.00) and also a higher fold expansion potential (11.893 ± 1.712) compared to the other groups. These cells once activated with IL-15, demonstrated a higher cytotoxicity against K562 (≥ 90%; P ≤ 0.001) and SKOV3 tumor cells (≥ 65%; P ≤ 0.001) compared to IL-15/Hsp70-activated NK cells.

conclusionsThe differentiation of ex vivo expanded CD34 + cells through manipulation of RAS/MAPK, IGF-1R and TGF-β signaling pathways is an efficient approach for generating functional NK cells that can be used for cancer immunotherapy.

Indexed as

Cancer immunotherapyCytotoxicityDifferentiationNatural killer cellsUmbilical cord blood

Identifiers

PMID34098947
PMCPMC8185927
OpenAlexW3105208797

What OpenQuestion holds

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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.