期刊
CANCERS
卷 12, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/cancers12092417
关键词
TIM-3; NK cell receptor; immunotherapy; solid tumor; NK cell activation
类别
资金
- Purdue Center for Cancer Research, NIH [P30 CA023168]
Among natural killer (NK) cell receptors, the T-cell immunoglobulin and mucin-containing domain (TIM-3) has been associated with both inhibitory and activating functions, depending on context and activation pathway. Ex vivo and in vitro, expression of TIM-3 is inducible and depends on activation stimulus. Here, we report that TIM-3 expression can be downregulated on NK cells under specific conditions. When NK cells are exposed to cancer targets, they synergize with stimulation conditions to induce a substantial decrease in TIM-3 expression on their surface. We found that such downregulation occurs following prior NK activation. Downregulated TIM-3 expression correlated to lower cytotoxicity and lower interferon gamma (IFN-gamma) expression, fueling the notion that TIM-3 might function as a benchmark for human NK cell dysfunction.
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