ArticleOncogene2018
Tumor cell-intrinsic Tim-3 promotes liver cancer via NF-κB/IL-6/STAT3 axis.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Prognostic Values of TIM-3 Expression in Patients With Solid Tumors: A Meta-Analysis and Database Evaluation.Frontiers in oncology · 2020Pooled it
- Therapeutic potential of targeting macrophage polarization in metastatic gastric cancer: a review on core mechanisms and clinical progress.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Review
- Immune checkpoint TIM-3 in tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- A Machine Learning-Based Nomogram for Predicting Overall Survival in BCLC Stage 0-B Hepatocellular Carcinoma Patients with Low HALP Score.Journal of inflammation research · 2026Article
- TIM-3 Promotes Proliferation of Acute Myeloid Leukemia Blasts.Biomedicines · 2025Article
- The role of immune checkpoints in modulating cancer stem cells anti-tumor immune responses: implications and perspectives in cancer therapy.Journal of experimental & clinical cancer research : CR · 2025Review
- The concurrent silencing of Tim-3 and STAT-3 promotes tumor regression both in vitro and in ovo.BMC cancer · 2025Article
- The Diverse Function of IL-6 in Biological Processes and the Advancement of Cancer.Immune network · 2025Review
- Review
- TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives.Molecular biomedicine · 2025Review
- The role of immune checkpoint molecules in cancers.Frontiers in immunology · 2025Review
- Transarterial Chemoembolization Following Curative Resection May Not Improve Survival for Hepatitis B Virus Associated Intrahepatic Cholangiocarcinoma: Propensity Score Weighting Analysis.Journal of hepatocellular carcinoma · 2025Article
- Soluble Tim-3 serves as a tumor prognostic marker and therapeutic target for CD8Cell reports. Medicine · 2024Article
- Combination of locoregional radiotherapy with a TIM-3 aptamer improves survival in diffuse midline glioma models.JCI insight · 2024Article
- Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.Journal of hematology & oncology · 2024Review
- Unveiling Tim-3 immune checkpoint expression in hepatocellular carcinoma through abdominal contrast-enhanced CT habitat radiomics.Frontiers in oncology · 2024Article
- Multiple myeloma and the potential of new checkpoint inhibitors for immunotherapy.Therapeutic advances in vaccines and immunotherapy · 2024Review
- Integrating Network Pharmacology and Experimental Validation to Decipher the Mechanism of Action ofDrug design, development and therapy · 2024Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-cell immunoglobulin and mucin-domain containing-3 (Tim-3), mediating immune exhaustion in tumor microenvironment, has become a promising target for tumor therapy. However, the exact mechanisms for tumor cell-intrinsic Tim-3 in tumor development and its potential contribution in Tim-3-targeted therapy strategy have not been elucidated yet. In this study, we showed that human liver cancer tissues contained high ratio of Tim-3-expressing hepatocytes, and cytokines rich in tumor microenvironment and HBV involved in Tim-3 upregulation in malignant hepatocytes. We demonstrated that hepatocyte-specific Tim-3 overexpression enhances tumor cell growth, whereas Tim-3 inhibition on malignant hepatocytes by anti-Tim-3 antibodies or RNAi suppresses tumor growth both in vitro and in Tim-3 knockout mice. Mechanistically, the hepatocyte-Tim-3 receptor activates NF-κB phosphorylation, which in turn stimulates IL-6 secretion and STAT3 phosphorylation. Our results identify tumor cell-intrinsic functions of Tim-3 in tumorigenesis and suggest that blocking Tim-3 in tumor cells might contribute to the clinical efficacy of anti-Tim-3 antibody treatment in the future tumor therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.