期刊
JOURNAL OF IMMUNOLOGY
卷 206, 期 4, 页码 677-685出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2000177
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资金
- National Institutes of Health [CA210087, CA068458, CA163205]
- City of Hope's Eugene and Ruth Roberts Summer Student Academy
The study revealed that Cbl-b is significantly upregulated in primary human NK cells activated by IL-15, IL-2, and K562, and downregulation of Cbl-b enhanced the anti-tumor effector functions of NK cells.
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-gamma 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.
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