TIM-3 Expression Is Downregulated on Human NK Cells in Response to Cancer Targets in Synergy with Activation

Tram N Dao; Sagar Utturkar; Nadia Atallah Lanman; Sandro Matosevic

doi:10.3390/cancers12092417

TIM-3 Expression Is Downregulated on Human NK Cells in Response to Cancer Targets in Synergy with Activation

Cancers (Basel). 2020 Aug 26;12(9):2417. doi: 10.3390/cancers12092417.

Authors

Tram N Dao¹, Sagar Utturkar², Nadia Atallah Lanman^{2

3}, Sandro Matosevic^{1

2}

Affiliations

¹ Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA.
² Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
³ Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA.

Abstract

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-γ) expression, fueling the notion that TIM-3 might function as a benchmark for human NK cell dysfunction.

Keywords: NK cell activation; NK cell receptor; TIM-3; immunotherapy; solid tumor.

Abstract

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