ArticleFrontiers in oncology2022
Monocarboxylate transporter upregulation in induced regulatory T cells promotes resistance to anti-PD-1 therapy in hepatocellular carcinoma patients.
Article in Frontiers in oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 20 citations in OpenAlex.
- Review
- Beyond a waste product: lactate as a master metabolite dictating anti-tumor T-cell fate.Cell death & disease · 2026Review
- Review
- Mechanisms of lactylation modification in hepatocellular carcinoma treatment resistance.Gastroenterology report · 2026Review
- Metabolic reprogramming-driven resistance to multi-kinase inhibitors in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities.Molecular cancer · 2026Review
- Lactylation in cancer: molecular mechanisms and advances in clinical study.Molecular cancer · 2026Review
- Immunometabolic Gatekeeping: Reconciling Peto's & the T-cell Infiltration Prognostic Paradox.ArXiv · 2025Article
- Targeting Lactylation: From Metabolic Reprogramming to Precision Therapeutics in Liver Diseases.Biomolecules · 2025Review
- Causal role of immune cells in primary liver cancer: a mendelian randomization study.BMC cancer · 2025Article
- Regulatory T Cell Metabolism: A Promising Therapeutic Target for Cancer Treatment?Immune network · 2025Review
- The role of MCT1 in tumor progression and targeted therapy: a comprehensive review.Frontiers in immunology · 2025Review
- Impact of lactate on immune cell function in the tumor microenvironment: mechanisms and therapeutic perspectives.Frontiers in immunology · 2025Review
- Lactate and lactylation in liver diseases: energy metabolism, inflammatory immunity and tumor microenvironment.Frontiers in immunology · 2025Review
- Taurine-Modified Gossypol Exerts Dual Anti-Hepatocellular Carcinoma Effects by Inactivating PI3K/AKT Pathway and Targeting FASN-Mediated Lipid Metabolism in Regulatory T Cells.Journal of hepatocellular carcinoma · 2025Article
- Lactylation: the malignant playbook of hepatocellular carcinoma cells and their roadmap to therapy resistance.Frontiers in immunology · 2025Review
- Revisiting of Cancer Immunotherapy: Insight from the Dialogue between Glycolysis and PD-1/PD-L1 Axis in the Tumor Microenvironment.International journal of biological sciences · 2025Review
- Role of lactate and lactate metabolism in liver diseases (Review).International journal of molecular medicine · 2024Review
- Expression of the monocarboxylate transporter MCT1 is required for virus-specific mouse CD8Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
- Research progress of abnormal lactate metabolism and lactate modification in immunotherapy of hepatocellular carcinoma.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Programmed cell death-1 (PD-1) immune checkpoint inhibitors are not effective in treating all patients with hepatocellular carcinoma (HCC), and regulatory T cells (Tregs) may determine the resistance to anti-PD-1 therapy. Methods: Patients were divided into two groups based on the clinical efficacy of anti-PD-1 therapy. Flow cytometry was used to determine the phenotype of CD4+, CD8+, and Tregs in peripheral blood mononuclear cells (PBMCs). CD4+CD45RA+T cells were sorted to analyze Treg differentiation and function. Results: No significant differences were found between resistant and sensitive patients in the percentage of CD4+ T cells and Tregs in PBMCs or the differentiation and function of induced Tregs (iTregs). However, iTregs from resistant patients presented higher monocarboxylate transporter (MCT) expression. Lactate induced more iTregs and improved OXPHOS levels in the resistant group. MCT1 and MCT2 were highly expressed in tumor-infiltrating Tregs, and patients with higher MCT1 expression had worse clinical outcomes. Combinatorial therapy with MCT antibody and anti-PD-1 therapy effectively inhibited tumor growth. Conclusion: MCT and its downstream lactate signal in Tregs can confer anti-PD-1 resistance and may be a marker of poor prognosis in HCC.
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