Pediatric multicellular tumor spheroid models illustrate a therapeutic potential by combining BH3 mimetics with Natural Killer (NK) cell-based immunotherapy.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
10 Jan 2022
10 Jan 2022
Historique:
received:
29
09
2021
accepted:
16
12
2021
revised:
03
12
2021
entrez:
11
1
2022
pubmed:
12
1
2022
medline:
12
1
2022
Statut:
epublish
Résumé
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
Identifiants
pubmed: 35013156
doi: 10.1038/s41420-021-00812-6
pii: 10.1038/s41420-021-00812-6
pmc: PMC8748928
doi:
Types de publication
Journal Article
Langues
eng
Pagination
11Subventions
Organisme : Deutsche Krebshilfe (German Cancer Aid)
ID : 70113791
Organisme : Deutsche Krebshilfe (German Cancer Aid)
ID : 70113791
Organisme : Deutsche Krebshilfe (German Cancer Aid)
ID : 70112823
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : CRC 1292 - IRTG
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : INST 256/423-1 FUGG
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : CRC 1292
Informations de copyright
© 2022. The Author(s).
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