Cbl-b Is Upregulated and Plays a Negative Role in Activated Human NK Cells.
J Immunol
; 206(4): 677-685, 2021 02 15.
Article
in En
| MEDLINE
| ID: mdl-33419766
ABSTRACT
The E3 ubiquitin ligase Cbl-b has been characterized as an intracellular checkpoint in T cells; however, the function of Cbl-b in primary human NK cells, an innate immune anti-tumor effector cell, is not well defined. In this study, we show that the expression of Cbl-b is significantly upregulated in primary human NK cells activated by IL-15, IL-2, and the human NK cell-sensitive tumor cell line K562 that lacks MHC class I expression. Pretreatment with JAK or AKT inhibitors prior to IL-15 stimulation reversed Cbl-b upregulation. Downregulation of Cbl-b resulted in significant increases in granzyme B and perforin expression, IFN-γ production, and cytotoxic activity against tumor cells. Collectively, we demonstrate upregulation of Cbl-b and its inhibitory effects in IL-15/IL-2/K562-activated human NK cells, suggesting that Cbl-b plays a negative feedback role in human NK cells.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Killer Cells, Natural
/
Adaptor Proteins, Signal Transducing
/
Proto-Oncogene Proteins c-cbl
/
Immune Checkpoint Proteins
Limits:
Humans
Language:
En
Journal:
J Immunol
Year:
2021
Type:
Article