ArticleCell reports. Medicine2024
Disruption of MerTK increases the efficacy of checkpoint inhibitor by enhancing ferroptosis and immune response in hepatocellular carcinoma.
Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 58 citations in OpenAlex.
- Harnessing copper-iron crosstalk: A novel strategy to combat hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- MERTK inhibition cooperates with immunomodulatory cyclophosphamide to induce CXCL9⁺ monocyte-macrophage programming and durable antitumor immunity in triple negative breast cancer.Cancer immunology research · 2026Article
- Enzyme-Guided Assembly Enables Precision Delivery of a Singlet Oxygen Battery for Membrane Lipid Peroxidation Therapy.Angewandte Chemie (International ed. in English) · 2026Article
- Disrupting fumarylacetoacetate hydrolase by stratified nanoplatforms orchestrates metabolic-immune reprogramming and prevents post-ablation HCC relapse.Nature communications · 2026Article
- The increased co-expression of SLC7A11 and PD-L1 was associated with poor prognosis in extranodal natural killer T-cell lymphoma patients.Cancer immunology, immunotherapy : CII · 2026Article
- Targeting ferroptosis induction via nanomaterials in hepatocellular carcinoma: an insight into mechanism and therapeutic potential.Journal of nanobiotechnology · 2026Review
- Macrophage MERTK restrains GRAMD1A-driven mitochondrial oxysterol trafficking to limit colitis.Redox biology · 2026Article
- Article
- "Ferroptosis-immune" cycle: Research progress of tumor microenvironment responsive nanomaterials in the treatment of pancreatic cancer.iScience · 2026Review
- TMEM87A suppresses ferroptosis and increases cancer immunotherapy resistance by maintaining the Golgi apparatus pH homeostasis.Nature cancer · 2026Article
- MerTK inhibition by UNC569 triggers DNA damage and JNK/p38 MAPK cascade-driven apoptosis in pancreatic cancer.Acta biochimica et biophysica Sinica · 2026Article
- Mechanism of FOXP2 in the Hepatocellular Carcinoma Progression via Ferroptosis Through RBM15B-Mediated m6A Modification.Applied biochemistry and biotechnology · 2026Article
- Overcoming MDSC-Mediated Immunosuppression in Hepatocellular Carcinoma: From Mechanisms to Novel Immunotherapeutic Approaches.Cancers · 2026Review
- AGPAT3 reshapes tumor cell vulnerability to IFNγ-mediated ferroptosis and enhances immunotherapy efficacy through lipid remodeling.Journal for immunotherapy of cancer · 2026Article
- MERTK inhibition cooperates with immunomodulatory cyclophosphamide to induce CXCL9bioRxiv : the preprint server for biology · 2026Article
- Ferroptosis in biliary tract cancer: Molecular mechanisms and therapeutic applications (Review).International journal of oncology · 2026Review
- Post-Translational Modification Networks in Ferroptosis: Orchestrating Defense, Drug Resistance, and Therapeutic Opportunities in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Review
- Genetic variants ofFrontiers in immunology · 2026Article
- Overcoming immune resistance in hepatocellular carcinoma: insights into mechanisms, predictive factors, and interventional strategies.Frontiers in immunology · 2026Review
- The Dual Role of SLC7A11 in Colorectal Cancer Ferroptosis: From Molecular Mechanisms to Therapeutic Opportunities.OncoTargets and therapy · 2026Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint inhibitors, particularly PD-1/PD-L1 blockades, have been approved for unresectable hepatocellular carcinoma (HCC). However, high resistance rates still limit their efficacy, highlighting the urgent need to understand the underlying mechanisms and develop strategies for overcoming the resistance. In this study, we demonstrate that HCC with high MER proto-oncogene tyrosine kinase (MerTK) expression exhibits anti-PD-1/PD-L1 resistance in two syngeneic mouse models and in patients who received anti-PD-1/PD-L1 therapy. Mechanistically, MerTK renders HCC resistant to anti-PD-1/PD-L1 by limiting ferroptosis with the upregulation of SLC7A11 via the ERK/SP1 pathway and facilitating the development of an immunosuppressive tumor microenvironment (TME) with the recruitment of myeloid-derived suppressor cells (MDSCs). Sitravatinib, an inhibitor of MerTK, sensitizes resistant HCC to anti-PD-L1 therapy by promoting tumor ferroptosis and decreasing MDSC infiltration into the TME. In conclusion, we find that MerTK could serve as a predictive biomarker for patient stratification and as a promising target to overcome anti-PD-1/PD-L1 resistance in HCC.
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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.