ArticleJournal for immunotherapy of cancer2025
Differential impact of TIM-3 ligands on NK cell function.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Natural killer cells against viral infection: from basic biology to immunotherapy.Precision clinical medicine · 2026Review
- Limited Clinical Benefit of Immune Checkpoint Inhibition in Ovarian Cancer with Opportunities in Selected Subtypes.International journal of molecular sciences · 2026Review
- LGALS9 blockade augments vaccine-induced immune responses against prostate cancer.Journal for immunotherapy of cancer · 2026Article
- Radiation-induced MYB reduction unleashes TIM-3 expression in NK cells to attenuate antitumor immunity in colorectal cancer.Journal of translational medicine · 2026Article
- CLL-1: An emerging target for immunotherapy in acute myeloid leukemia.Annals of hematology · 2026Review
- Distinct NK Cell Signatures Define Prognosis in HPV-Positive Versus HPV-Negative Head and Neck Cancer.Cancers · 2026Article
- Comprehensive immune profiling of human peripheral blood mononuclear cells using two complementary spectral flow cytometry panels encompassing 60 unique markers.Frontiers in immunology · 2026Article
- Inhibitory immune checkpoints in preeclampsia: current landscape, mechanisms, and clinical perspectives.Frontiers in immunology · 2026Review
- Immune checkpoint TIM-3 defines hyperactivated NK cells and predicts fatal outcome in severe fever with thrombocytopenia syndrome.PLoS neglected tropical diseases · 2026Article
- Multidimensional plasticity of natural killer cells in tumours.Cell death & disease · 2025Review
- Impact of HMGA1 on tumorigenesis, prognosis and immune microenvironment in HNSCC: a multi-omics study.NPJ precision oncology · 2025Article
- Commentary on differential impact of TIM-3 ligands on NK cell function.Journal for immunotherapy of cancer · 2025Article
- Tumor Microenvironment, Inflammation, and Inflammatory Prognostic Indices in Diffuse Large B-Cell Lymphomas: A Narrative Review.International journal of molecular sciences · 2025Review
- Serum soluble Tim‑3 is elevated in patients with cervical cancer and is higher in advanced clinical stages.Biomedical reports · 2025Article
- The Role of NK Cells in Cancer Immunotherapy: Mechanisms, Evasion Strategies, and Therapeutic Advances.Biomedicines · 2025Review
- Multi-omics in immunotherapy research for HNSCC: present situation and future perspectives.NPJ precision oncology · 2025Review
- NK cells in HPV-related tumorigenesis: mechanisms and clinical applications.Frontiers in cellular and infection microbiology · 2025Review
- Adherent Natural Killer Cells De Novo Express IL-2Rα and Sustain Long-Lasting, Potent Anti-Tumor Activity in Picomolar Concentrations of IL-2.Journal of cancer immunology · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
backgroundThe transmembrane protein T-cell immunoglobulin and mucin-domain containing molecule 3 (TIM-3) is an immune checkpoint receptor that is expressed by a variety of leukocyte subsets, particularly in the tumor microenvironment. An effective TIM-3-targeting therapy should account for multiple biological factors, including the disease setting, the specific cell types involved and their varying sensitivities to the four putative TIM-3 ligands (galectin-9, phosphatidylserine, high mobility group protein B1 and carcinoembryonic antigen cell adhesion molecule 1), each of which engages a unique binding site on the receptor's variable immunoglobulin domain. The primary objectives of this study were to assess the prevalence and function of TIM-3
methodsSingle-cell RNA sequencing and flow cytometry were used to study the prevalence, phenotypes and function of TIM-3
resultsWe demonstrate that TIM-3 is highly prevalent on circulating and tumor-infiltrating NK cells. It co-expresses with CD44 and marks NK cells with heightened effector potential. Among the four putative TIM-3 ligands, galectin-9 most consistently suppresses NK cell-mediated cytotoxicity and proliferation through TIM-3 and CD44 signaling, respectively, but promotes IFN-γ release in a TIM-3-dependent manner. Among patients with HNSCC, an elevated intratumoral TIM-3
conclusionsOur findings underscore the complex functional impact of TIM-3 ligand signaling, which is consistent with recent clinical trials suggesting that targeting TIM-3 alone is suboptimal as an immunotherapeutic approach for treating malignancies.
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