Evidence map›Paper›PMID 35013156›Full record

ArticleCell death discovery2022

Pediatric multicellular tumor spheroid models illustrate a therapeutic potential by combining BH3 mimetics with Natural Killer (NK) cell-based immunotherapy.

Vinzenz Särchen, Senthan Shanmugalingam, Sarah Kehr, Lisa Marie Reindl, Victoria Greze, Sara Wiedemann, Cathinka Boedicker, Maureen Jacob, Katrin Bankov, Nina Becker and 7 more

Open access · goldAbstract read
In one paragraph

Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 15% 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, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Immune organoid for cancer immunotherapy.Acta pharmaceutica Sinica. B · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Frontiers in immunology · 2023
    Review
  14. Review
  15. Mitochondrial apoptosis: facilitator of NK cell-mediated immunotherapy.Signal transduction and targeted therapy · 2022
    Article
  16. Evaluating immune responseExploration of targeted anti-tumor therapy · 2022
    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

17 authors at 2 institutions in 1 country.

Vinzenz Särchen *Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Frankfurt am Main, Germany.ORCID http://orcid.org/0000-0001-9565-2850
Senthan Shanmugalingam *Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Sarah Kehr *Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Lisa Marie ReindlChildren's Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany.ORCID http://orcid.org/0000-0002-1027-1256
Victoria GrezeChildren's Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Sara WiedemannInstitute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Cathinka BoedickerInstitute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Maureen JacobInstitute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Katrin BankovDr. Senckenberg Institute of Pathology, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Nina BeckerDr. Senckenberg Institute of Pathology, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Sibylle WehnerChildren's Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Till M TheilenDepartment of Pediatric Surgery and Pediatric Urology, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Steffen GretserDepartment of Pediatric and Perinatal Pathology, Dr. Senckenberg Institute of Pathology, Goethe-University Frankfurt, Frankfurt am Main, Germany.ORCID http://orcid.org/0000-0002-4875-3808
Elise GradhandDepartment of Pediatric and Perinatal Pathology, Dr. Senckenberg Institute of Pathology, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Carsten KummerowDepartment of Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, Homburg, Saarland, Germany.ORCID http://orcid.org/0000-0001-5667-2293
Evelyn UllrichChildren's Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Meike VoglerInstitute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Frankfurt am Main, Germany. m.vogler@kinderkrebsstiftung-frankfurt.de.ORCID http://orcid.org/0000-0003-2650-586X
Goethe University Frankfurt · DESaarland University · DE

Funding

Deutsche Forschungsgemeinschaft (German Research Foundation) CRC 1292Deutsche Forschungsgemeinschaft (German Research Foundation) CRC 1292 - IRTGDeutsche Forschungsgemeinschaft (German Research Foundation) INST 256/423-1 FUGGDeutsche Krebshilfe (German Cancer Aid) 70112823Deutsche Krebshilfe (German Cancer Aid) 70113791
6 · The paper itself

Abstract

The induction of apoptosis is a direct way to eliminate tumor cells and improve cancer therapy. Apoptosis is tightly controlled by the balance of pro- and antiapoptotic Bcl-2 proteins. BH3 mimetics neutralize the antiapoptotic function of Bcl-2 proteins and are highly promising compounds inducing apoptosis in several cancer entities including pediatric malignancies. However, the clinical application of BH3 mimetics in solid tumors is impeded by the frequent resistance to single BH3 mimetics and the anticipated toxicity of high concentrations or combination treatments. One potential avenue to increase the potency of BH3 mimetics is the development of immune cell-based therapies to counteract the intrinsic apoptosis resistance of tumor cells and sensitize them to immune attack. Here, we describe spheroid cultures of pediatric cancer cells that can serve as models for drug testing. In these 3D models, we were able to demonstrate that activated allogeneic Natural Killer (NK) cells migrated into tumor spheroids and displayed cytotoxicity against a wide range of pediatric cancer spheroids, highlighting their potential as anti-tumor effector cells. Next, we investigated whether treatment of tumor spheroids with subtoxic concentrations of BH3 mimetics can increase the cytotoxicity of NK cells. Notably, the cytotoxic effects of NK cells were enhanced by the addition of BH3 mimetics. Treatment with either the Bcl-X

Identifiers

PMID35013156
PMCPMC8748928
OpenAlexW4206816069

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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.