Commentary on differential impact of TIM-3 ligands on NK cell function

T-cell immunoglobin and mucin-domain containing molecule 3 (TIM-3) is an immune checkpoint receptor and a target for immune checkpoint blockers (ICBs). Unfortunately in human patients the success rate of anti-TIM-3 ICB remains rather limited. Multiple immune cells express TIM-3 and their functioning...

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Main Author: Rieneke van de Ven
Format: Article
Language:English
Published: BMJ Publishing Group 2025-07-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/13/7/e012125.full
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author Rieneke van de Ven
author_facet Rieneke van de Ven
author_sort Rieneke van de Ven
collection DOAJ
description T-cell immunoglobin and mucin-domain containing molecule 3 (TIM-3) is an immune checkpoint receptor and a target for immune checkpoint blockers (ICBs). Unfortunately in human patients the success rate of anti-TIM-3 ICB remains rather limited. Multiple immune cells express TIM-3 and their functioning is affected by receptor–ligand interactions. Four ligands of TIM-3 have been identified: high-mobility group protein B1, galectin-9, phosphatidylserine and carcinoembryonic antigen cell adhesions molecule 1. Wang et al investigated which of these ligands interact with TIM-3 on natural killer (NK) cells, impairing NK cytotoxicity and proliferation. They demonstrated that galectin-9 was able to inhibit NK cell cytotoxicity in a TIM-3-dependent manner, and to block NK cell proliferation through interaction with CD44 on NK cells. They also showed that in head and neck squamous cell carcinoma (HNSCC), a high TIM-3+NK cell transcriptional signature was linked to poor survival probability, specifically in HNSCC caused by human papillomavirus infection. This study enhances our understanding of why anti-TIM-3 ICB may not be so effective as monotherapy and provides leads toward rational design of combination strategies and patient selection.
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spelling doaj-art-1e2cebaad1834b8f9d06de86465d2f4c2025-08-20T02:36:35ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-07-0113710.1136/jitc-2025-012125Commentary on differential impact of TIM-3 ligands on NK cell functionRieneke van de Ven0Otolaryngology/Head and Neck Surgery, Amsterdam UMC—Locatie VUMC, Amsterdam, The NetherlandsT-cell immunoglobin and mucin-domain containing molecule 3 (TIM-3) is an immune checkpoint receptor and a target for immune checkpoint blockers (ICBs). Unfortunately in human patients the success rate of anti-TIM-3 ICB remains rather limited. Multiple immune cells express TIM-3 and their functioning is affected by receptor–ligand interactions. Four ligands of TIM-3 have been identified: high-mobility group protein B1, galectin-9, phosphatidylserine and carcinoembryonic antigen cell adhesions molecule 1. Wang et al investigated which of these ligands interact with TIM-3 on natural killer (NK) cells, impairing NK cytotoxicity and proliferation. They demonstrated that galectin-9 was able to inhibit NK cell cytotoxicity in a TIM-3-dependent manner, and to block NK cell proliferation through interaction with CD44 on NK cells. They also showed that in head and neck squamous cell carcinoma (HNSCC), a high TIM-3+NK cell transcriptional signature was linked to poor survival probability, specifically in HNSCC caused by human papillomavirus infection. This study enhances our understanding of why anti-TIM-3 ICB may not be so effective as monotherapy and provides leads toward rational design of combination strategies and patient selection.https://jitc.bmj.com/content/13/7/e012125.full
spellingShingle Rieneke van de Ven
Commentary on differential impact of TIM-3 ligands on NK cell function
Journal for ImmunoTherapy of Cancer
title Commentary on differential impact of TIM-3 ligands on NK cell function
title_full Commentary on differential impact of TIM-3 ligands on NK cell function
title_fullStr Commentary on differential impact of TIM-3 ligands on NK cell function
title_full_unstemmed Commentary on differential impact of TIM-3 ligands on NK cell function
title_short Commentary on differential impact of TIM-3 ligands on NK cell function
title_sort commentary on differential impact of tim 3 ligands on nk cell function
url https://jitc.bmj.com/content/13/7/e012125.full
work_keys_str_mv AT rienekevandeven commentaryondifferentialimpactoftim3ligandsonnkcellfunction