ArticleClinical and molecular hepatology2025
CD36 promotes iron accumulation and dysfunction in CD8+ T cells via the p38-CEBPB-TfR1 axis in early-stage hepatocellular carcinoma.
Article in Clinical and molecular hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Adjuvant cytokine-induced killer cell immunotherapy in hepatocellular carcinoma: real-world data and 9-year extended follow-up of a randomized controlled trial.Cancer immunology, immunotherapy : CII · 2026Trial
- Lipid metabolic reprogramming of tumor-associated macrophages drives resistance to immune checkpoint blockade in lung cancer: a narrative review of mechanisms and therapeutic strategies.Translational lung cancer research · 2026Review
- Review
- Advances in Lipid Metabolism Reprogramming in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Correspondence to editorial on "Dysfunction in CD8+ T cells in early-stage HCC": New insights into HCC immunotherapy: Letter to the editor on "CD36 promotes iron accumulation and dysfunction in CD8+ T cells via the p38-CEBPB-TfR1 axis in early-stage hepatocellular carcinoma".Clinical and molecular hepatology · 2026Article
- T-Cell Exhaustion in the Tumor Microenvironment: Subcellular Dysfunction, Pan-Cancer Characteristics, and Therapeutic Interventions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Decoding the spatiotemporal characteristics of ferroptosis: reshaping tumour therapeutic strategies.Experimental hematology & oncology · 2026Review
- CD8Cancer cell international · 2026Review
- Reprogrammed Lipid Metabolism as a Gatekeeper of Hepatocarcinogenesis: from Enzyme Regulation to Precision Therapy.Current oncology reports · 2026Review
- Senescent fibroblasts drive CD8Journal of translational medicine · 2026Article
- The Role of Low CD36 Expression in the Development of Non-Small Cell Lung Cancer and Its Potential for Therapy.Cancers · 2026Review
- Metabolic Barriers to Cancer Immunotherapy: Multiscale Mechanisms from Organelle Dysfunction to Organ-Specific Constraints.International journal of biological sciences · 2026Review
- Nanomaterials Reshaping Tumor Metabolism: A New Frontier to Overcome T Cell Exhaustion.International journal of nanomedicine · 2026Review
- Correspondence to editorial on "CD36 Promotes iron accumulation and dysfunction in CD8+ T cells via the p38-CEBPB-TfR1 axis in early-stage hepatocellular carcinoma".Clinical and molecular hepatology · 2026Article
- AI-integrated single-cell multi-omics decodes the hepatocellular carcinoma metabolism-immune axis: a new strategy for precision therapeutic targeting.Frontiers in oncology · 2026Review
- Targeting CD36 to reinvigorate CD8+ T Cells in early-stage hepatocellular carcinoma: Editorial on "CD36 promotes iron accumulation and dysfunction in CD8+ T cells via the p38-CEBPB-TfR1 axis in early-stage hepatocellular carcinoma".Clinical and molecular hepatology · 2026Article
- Can tissue immune states shape the risk of hyperprogressive disease?Frontiers in immunology · 2026Review
- NEFA Promotes Bovine Granulosa Cell Apoptosis via Activation of the PERK/eIF2α/ATF4/CHOP Pathway.Veterinary sciences · 2025Article
- Ferroptosis in cancer: metabolism, mechanisms and therapeutic prospects.Molecular cancer · 2025Review
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24 authors.
Funding
Abstract
BACKGROUND/
aimsThe identification of factors that lead to CD8+ T cell dysfunction within the tumor microenvironment (TME) holds great promise for the development of innovative immunotherapies. However, the mechanisms underlying the exhausted phenotype of CD8+ T cells infiltrating early-stage hepatocellular carcinoma (HCC) tumors remain unclear.
methodsSingle-cell RNA sequencing was performed using a murine HCC model. Flow cytometry and additional experimental approaches were employed to investigate the mechanisms of CD8+ T cell exhaustion.
resultsCD8+ T cells infiltrating early-stage HCC exhibited a functionally exhausted phenotype, which escalated with HCC progression. At early stages of HCC, the TME was characterized by significant iron accumulation. Moreover, tumor-infiltrating CD8+ T cells in murine HCC exhibited higher levels of intracellular ferrous iron compared to splenic CD8+ T. This excessive iron led to increased lipid peroxide levels and impaired the effector function of CD8+ T cells. Mechanistically, CD36 upregulated the iron uptake protein transferrin receptor 1 (TfR1) by mediating the activation of oxidized low-density lipoprotein (oxLDL)-p38-CEBPB axis. Depletion of CD36 in CD8+ T cells inhibited the upregulation of TfR1 and the increase of iron levels. Furthermore, constitutively activated nuclear factor erythroid 2-related factor 2 (NRF2) effectively suppressed lipid peroxidation, thereby preserving the effector functions of intratumoral CD8+ T cells and ultimately inhibiting tumor growth.
conclusionOur findings reveal a previously unidentified mechanism mediated by CD36 that regulates the progressive dysfunction of CD8+ T cells in early HCC TME and provide a potential novel therapeutic approach to restore T cell function.
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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.