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

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 sti...

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Autores principales: Dao, Tram N., Utturkar, Sagar, Atallah Lanman, Nadia, Matosevic, Sandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565804/
https://www.ncbi.nlm.nih.gov/pubmed/32858904
http://dx.doi.org/10.3390/cancers12092417
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author Dao, Tram N.
Utturkar, Sagar
Atallah Lanman, Nadia
Matosevic, Sandro
author_facet Dao, Tram N.
Utturkar, Sagar
Atallah Lanman, Nadia
Matosevic, Sandro
author_sort Dao, Tram N.
collection PubMed
description 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.
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spelling pubmed-75658042020-10-26 TIM-3 Expression Is Downregulated on Human NK Cells in Response to Cancer Targets in Synergy with Activation Dao, Tram N. Utturkar, Sagar Atallah Lanman, Nadia Matosevic, Sandro Cancers (Basel) Article 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. MDPI 2020-08-26 /pmc/articles/PMC7565804/ /pubmed/32858904 http://dx.doi.org/10.3390/cancers12092417 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dao, Tram N.
Utturkar, Sagar
Atallah Lanman, Nadia
Matosevic, Sandro
TIM-3 Expression Is Downregulated on Human NK Cells in Response to Cancer Targets in Synergy with Activation
title TIM-3 Expression Is Downregulated on Human NK Cells in Response to Cancer Targets in Synergy with Activation
title_full TIM-3 Expression Is Downregulated on Human NK Cells in Response to Cancer Targets in Synergy with Activation
title_fullStr TIM-3 Expression Is Downregulated on Human NK Cells in Response to Cancer Targets in Synergy with Activation
title_full_unstemmed TIM-3 Expression Is Downregulated on Human NK Cells in Response to Cancer Targets in Synergy with Activation
title_short TIM-3 Expression Is Downregulated on Human NK Cells in Response to Cancer Targets in Synergy with Activation
title_sort tim-3 expression is downregulated on human nk cells in response to cancer targets in synergy with activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565804/
https://www.ncbi.nlm.nih.gov/pubmed/32858904
http://dx.doi.org/10.3390/cancers12092417
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