ArticleCell reports. Medicine2025
ACVR2A attenuation impacts lactate production and hyperglycolytic conditions attracting regulatory T cells in hepatocellular carcinoma.
Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed.
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The Cancer Cell Metabolic Reprogramming Remodels the Tumor Microenvironment: Molecular Mechanisms and Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Solute carrier transporters as metabolic gatekeepers in tumor-microenvironment crosstalk.Acta pharmacologica Sinica · 2026Review
- H4K5 lactylation - ENO2 loop drives glycolysis and HCC progression.JHEP reports : innovation in hepatology · 2026Article
- NIPAL1 Drives a Metabolic-Epigenetic Feedback Loop to Promote Lactate-Mediated Immune Evasion in Esophageal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- LDHA-driven lactate metabolism promotes MDSC activation and immunosuppressive microenvironment in prostate cancer.Oncogene · 2026Article
- Regulation of immune tolerance in hepatocellular carcinoma by liver diseases: a review.Infectious agents and cancer · 2026Review
- Clinical Prediction of Glycolysis-Driven Molecular Subclass of Hepatocellular Carcinoma without Transcriptomic Profiling.Liver cancer · 2026Article
- <p>Beyond hepatic stellate cell heterogeneity: Resolving fibrosis, restoring regeneration (Review)</p>.International journal of molecular medicine · 2026Review
- The Role of CD4Cells · 2026Review
- Metabolic reprogramming-driven resistance to multi-kinase inhibitors in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities.Molecular cancer · 2026Review
- Etiology-Driven Mouse Models of Hepatocellular Carcinoma: Paving the Way for Precision Oncology.Journal of hepatocellular carcinoma · 2026Review
- Post-translational modification in hepatocellular carcinoma resistance: molecular mechanisms and therapeutic targeting.Frontiers in immunology · 2026Review
- Overcoming immune resistance in hepatocellular carcinoma: insights into mechanisms, predictive factors, and interventional strategies.Frontiers in immunology · 2026Review
- Drug resistance mechanisms of immunotherapy and translational strategies for reversing resistance for hepatocellular carcinoma: from bench to bedside.Frontiers in immunology · 2026Review
- Correspondence to editorial on "Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway".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
- Metabolic immune checkpoints in cancer: how tumor-derived metabolites shape immunotherapy resistance.Frontiers in immunology · 2026Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although ACVR2A mutations are prevalent in non-viral hepatocellular carcinomas (HCCs), the underlying mechanism remains unelucidated. Our molecular investigation reveals that ACVR2A impairment induces hyperglycolysis through the inactivation of the SMAD signaling pathway. Using syngeneic transplantation models and human clinical samples, we clarify that ACVR2A-deficient HCC cells produce and secrete lactate via the upregulation of lactate dehydrogenase A (LDHA) and monocarboxylate transporter 4 (MCT4) expression levels, which promotes regulatory T (Treg) cell accumulation and then acquires resistance to immune checkpoint inhibitors. Remarkably, genetic knockdown and pharmacological inhibition of MCT4 ameliorate the high-lactate milieu in ACVR2A-deficient HCC, resulting in the suppression of intratumoral Treg cell recruitment and the restoration of the sensitivity to PD-1 blockade. These findings furnish compelling evidence that lactate attenuates anti-tumor immunity and that therapeutics targeting this pathway present a promising strategy for mitigating immunotherapy resistance in ACVR2A-deficient HCC.
Indexed as
Identifiers
What OpenQuestion holds
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.