ArticleNature2016
NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 484 papers.
What it found
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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.
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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.
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Who cites it
484 citing papers in PubMed, 749 citations in OpenAlex.
- The Emerging Challenge of Non-Cirrhotic MASLD-Related Hepatocellular Carcinoma: Etiology, Immunopathology, and Precision Oncology.Liver cancer · 2026Review
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- ZFP90 Serves as a Transcriptional Brake on NF-κB Signaling to Attenuate Diet-Induced MASLD Progression.Nutrients · 2026Article
- Depletion of NAT10 in T cells attenuates metabolic dysfunction-associated steatohepatitis in mice.Hepatology communications · 2026Article
- Suppression of macrophage membrane cholesterol efflux by SLAMF7-induced IL-7 signaling improves immunotherapy efficacy in hepatocellular carcinoma.Hepatology international · 2026Article
- Etiology-Based Treatment for Unresectable/Advanced Hepatocellular Carcinoma: Focus on Viral Hepatitis and Metabolic Dysfunction-Associated Steatohepatitis.Liver cancer · 2026Review
- The versatile interplay between steatotic liver disease and liver cancer.Nature reviews. Cancer · 2026Review
- Germline mutations and somatic mosaicism in steatotic liver diseases and related liver carcinogenesis.Nature reviews. Gastroenterology & hepatology · 2026Review
- The association of newborn metabolites with early-life wheezing and asthma among US children in the ECHO Program.Communications medicine · 2026Article
- Pachymic Acid Alleviates Non-Alcoholic Fatty Liver Disease via FGF21-Mediated Inhibition of the p38 MAPK Pathway.Food science & nutrition · 2026Article
- Review
- [Research progress on poor response, resistance mechanisms, and influencing factors of immunotherapy for hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- The evidence for the use of peripheral blood indices in the diagnosis of breast cancer.The Journal of international medical research · 2026Review
- Systemic immune profiling uncovers divergent mechanisms and predictive biomarkers of response to combination immunotherapies in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- Review
- The Role of CD4Cells · 2026Review
- Identification of a Novel TIM-3 Targeting Peptides Probe to Indicate the Immunomodulation of SBRT Combined with Anti-TIM-3 Therapy in HCC.Molecular imaging and biology · 2026Article
- Pyruvate kinase muscle 2 (PKM2) promotes CD4 T cell survival by regulating pyruvate oxidation during homeostasis and expansion.Science advances · 2026Article
- The "Immune Rebellion" from the Intestines to the Liver: A Vicious Cycle That Causes the Liver to Collapse.Metabolites · 2026Review
- Article
424 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 7 institutions in 3 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Non-alcoholic fatty liver disease (NAFLD) affects a large proportion of the US population and is considered to be a metabolic predisposition to liver cancer. However, the role of adaptive immune responses in NAFLD-promoted HCC is largely unknown. Here we show, in mouse models and human samples, that dysregulation of lipid metabolism in NAFLD causes a selective loss of intrahepatic CD4(+) but not CD8(+) T lymphocytes, leading to accelerated hepatocarcinogenesis. We also demonstrate that CD4(+) T lymphocytes have greater mitochondrial mass than CD8(+) T lymphocytes and generate higher levels of mitochondrially derived reactive oxygen species (ROS). Disruption of mitochondrial function by linoleic acid, a fatty acid accumulated in NAFLD, causes more oxidative damage than other free fatty acids such as palmitic acid, and mediates selective loss of intrahepatic CD4(+) T lymphocytes. In vivo blockade of ROS reversed NAFLD-induced hepatic CD4(+) T lymphocyte decrease and delayed NAFLD-promoted HCC. Our results provide an unexpected link between lipid dysregulation and impaired anti-tumour surveillance.
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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.