ArticleMedicine2016
Immune checkpoint proteins PD-1 and TIM-3 are both highly expressed in liver tissues and correlate with their gene polymorphisms in patients with HBV-related hepatocellular carcinoma.
Article in Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 95 citations in OpenAlex.
- Advances in oncolytic viruses immunotherapy of hepatocellular carcinoma.Discover oncology · 2026Review
- Efficacy of Immune Checkpoint Inhibitors and Oncoviruses in Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Predictive Modeling and Mendelian Randomization for Identifying HCC Patients with High Response to TACE with Atezolizumab and Bevacizumab.Journal of hepatocellular carcinoma · 2026Article
- Review
- Natural killer cell therapy in hepatocellular carcinoma: a comprehensive review.Discover oncology · 2025Review
- Immunohistochemical Profiling of Immune Checkpoints in Chronic Hepatitis B Liver Tissue.Pathogens (Basel, Switzerland) · 2025Article
- Immune microenvironment and immunotherapy in hepatocellular carcinoma: mechanisms and advances.Frontiers in immunology · 2025Review
- Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients.Current medical science · 2024Article
- Association of mitochondrial phosphoenolpyruvate carboxykinase with prognosis and immune regulation in hepatocellular carcinoma.Scientific reports · 2024Article
- Progression of oncolytic virus in liver cancer treatment.Frontiers in oncology · 2024Review
- Intratumoral delivery of a Tim-3 antibody-encoding oncolytic adenovirus engages an effective antitumor immune response in liver cancer.Journal of cancer research and clinical oncology · 2023Article
- Advances in Immunotherapy for Hepatocellular Carcinoma (HCC).Current oncology (Toronto, Ont.) · 2023Review
- Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy.Journal of hematology & oncology · 2023Review
- Association of programmed cell death 1 (PD-1) gene polymorphism (rs10204525) with COVID-19 severity and mortality: A case-control study in the Iranian population.International immunopharmacology · 2023Article
- Review
- Evaluation of the possible association of PDCD-1 and LAG3 gene polymorphisms with hepatocellular carcinoma risk.BMC medical genomics · 2023Article
- Article
- Review
- Updates on the immunopathology and genomics of severe cutaneous adverse drug reactions.The Journal of allergy and clinical immunology · 2023Review
- Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma.Frontiers in immunology · 2023Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint proteins programmed death-1 (PD-1) and T-cell immunoglobulin domain and mucin domain containing molecule-3 (TIM-3) expression and their gene polymorphisms have separately been shown to be associated with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study simultaneously examined PD-1 and TIM-3 expression in liver tissues and PD1 and TIM3 polymorphisms and analyzed their correlations in 171 patients with HBV-related HCC and 34 patients with HBV-related cirrhosis.PD-1 and TIM-3 expression in liver tissues were examined by immunohistochemistry and the genotypes of PD1 rs10204525 and TIM3 rs10053538 polymorphisms were determined using genomic DNA extracted from peripheral blood as template.Both PD-1 and TIM-3 expressions in liver infiltrating lymphocytes of HCC tumor tissues were significantly higher than those in tumor adjacent tissues or cirrhotic tissues. The elevated PD-1 and TIM-3 expressions were significantly associated with higher tumor grades. The levels between PD-1 and TIM-3 expression in tumor tissues and tumor adjacent tissues had a significant positive intercorrelation. The expressions of PD-1 and TIM-3 in tumor tissues, tumor adjacent tissues, and cirrhotic tissues were significantly associated with PD1 and TIM3 polymorphisms, with genotype AA of PD1 rs10204525 and genotypes GT+TT of TIM3 rs10053538 being associated with significantly increased PD-1 and TIM-3 expression, respectively.These findings support the potential to improve the efficiency of immune checkpoint-targeted therapy and reduce resistance to the therapy by blocking both PD-1 and TIM-3 and suggest the potential to apply the genotype determination of PD1 rs10204525 and TIM3 rs10053538 as biomarkers of immune checkpoint-directed therapies.
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