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Showcasing the wonderful research of SDCPI Members

Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes In Vivo Persistence and Enhances Anti-tumor Activity

Huang Zhu, Robert H. Blum, Davide Bernareggi, Kun-Liang Guan, Karl-Johan Malmberg, Dan S. Kaufman


In Brief
CISH normally inhibits IL-15 signaling in
natural killer (NK) cells. Here, Zhu and
colleagues delete CISH expression in NK
cells derived from human induced
pluripotent stem cells (iPSCs). CISH/
iPSC-derived NK cells demonstrate
improved killing of tumor cells that is
directly attributable to a more efficient
metabolic profile.

Deletion of CISH in human NK cells leads to improved antitumor activity.
CISH/ NK cells demonstrate more efficient glycolytic and
OxPhos activity.
The improved metabolic profile is mediated by mTOR
CISH/ NK cells more effectively treat AML in vivo with
longer NK cell persistence.