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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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2025-07-01
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| 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. |
| format | Article |
| id | doaj-art-1e2cebaad1834b8f9d06de86465d2f4c |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| 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 |