ArticleJournal for immunotherapy of cancer2023
Single-cell RNA-sequencing atlas reveals an FABP1-dependent immunosuppressive environment in hepatocellular carcinoma.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 42 citations in OpenAlex.
- Review
- Single-cell RNA sequencing reveals immune microenvironment heterogeneity in BRCA1-mutated and sporadic triple-negative breast cancer.Translational oncology · 2026Article
- Single-Cell Transcriptomic Profiling Reveals Immunometabolic Reprogramming and Cell-Cell Communication in the Tumor Microenvironment of Human Hepatocellular Carcinoma.International journal of molecular sciences · 2026Article
- Fatty acid metabolic reprogramming in the tumor microenvironment: Unraveling mechanisms and therapeutic prospects.Genes & diseases · 2026Review
- Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment.Cellular & molecular immunology · 2026Review
- Mechanistic insights into CAR-mediated repression of the HNF4α-FABP1 axis and inhibition of HepG2 cell proliferation.Pharmacological research · 2026Article
- Characterization and regulatory mechanism evaluation of C8orf33 in hepatocellular carcinoma through multiomics profiling.Discover oncology · 2026Article
- Solute Carrier transporters in tumor metabolism and immune modulation: implications for therapy.Journal of translational medicine · 2026Review
- [Heterogeneity of tumor-associated macrophages and precision targeting strategies in hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Colorectal Cancer Cell's Weapon: RNF32 Engages SPP1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multi-omics analysis reveals that FABP2 suppresses colorectal cancer progression by regulating sphingomyelin metabolism via the PPAR signaling pathway.Cancer cell international · 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
- Aristolochic acid I accelerates lung adenocarcinoma progression coupled with the upregulation of core oncogenic networks: an integrated network toxicology and experimental study.Frontiers in pharmacology · 2026Article
- Single Cell RNA Sequencing in Colorectal Cancer Immunology: Recent Updates, Application, and Emerging Challenges.Current molecular medicine · 2026Review
- Integrative single-nucleus transcriptomic analysis identifies UBE2C+ proliferative tumor cells and immune-stromal regulatory crosstalk in small cell lung cancer.Frontiers in immunology · 2026Article
- Single-cell transcriptomic profile unveils distinct immune ecosystems in alcohol- and nonalcohol-associated hepatocellular carcinoma.Frontiers in immunology · 2026Article
- Research Progress on the Mechanisms of Traditional Chinese Medicine in Preventing and Treating HCC Invasion and Metastasis Based on Lipid Metabolic Reprogramming.Current topics in medicinal chemistry · 2026Review
- Tumor-associated macrophages in hepatocellular carcinoma: Cellular plasticity and therapy resistance in crosstalk.Journal of pharmaceutical analysis · 2026Review
- Single-cell landscape of melanoma reveals ETV5-driven C3 ID4Frontiers in immunology · 2026Article
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
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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
backgroundSingle-cell RNA sequencing, also known as scRNA-seq, is a method profiling cell populations on an individual cell basis. It is particularly useful for more deeply understanding cell behavior in a complicated tumor microenvironment. Although several previous studies have examined scRNA-seq for hepatocellular carcinoma (HCC) tissues, no one has tested and analyzed HCC with different stages.
methodsIn this investigation, immune cells isolated from surrounding normal tissues and cancer tissues from 3 II-stage and 4 III-stage HCC cases were subjected to deep scRNA-seq. The analysis included 15 samples. We distinguished developmentally relevant trajectories, unique immune cell subtypes, and enriched pathways regarding differential genes. Western blot and co-immunoprecipitation were performed to demonstrate the interaction between fatty acid binding protein 1 (FABP1) and peroxisome proliferator-activated receptor gamma(PPARG). In vivo experiments were performed in a C57BL/6 mouse model of HCC established via subcutaneous injection.
resultsFABP1 was discovered to be overexpressed in tumor-associated macrophages (TAMs) with III-stage HCC tissues compared with II-stage HCC tissues. This finding was fully supported by immunofluorescence detection in significant amounts of HCC human samples. FABP1 deficiency in TAMs inhibited HCC progression in vitro. Mechanistically, FABP1 interacted with PPARG/CD36 in TAMs to increase fatty acid oxidation in HCC. When compared with C57BL/6 mice of the wild type, tumors in FABP1-/- mice consistently showed attenuation. The FABP1-/- group's relative proportion of regulatory T cells and natural killer cells showed a downward trend, while dendritic cells, M1 macrophages, and B cells showed an upward trend, according to the results of mass cytometry. In further clinical translation, we found that orlistat significantly inhibited FABP1 activity, while the combination of anti-programmed cell death 1(PD-1) could synergistically treat HCC progression. Liposomes loaded with orlistat and connected with IR780 probe could further enhance the therapeutic effect of orlistat and visualize drug metabolism in vivo.
conclusionsScRNA-seq atlas revealed an FABP1-dependent immunosuppressive environment in HCC. Orlistat significantly inhibited FABP1 activity, while the combination of anti-PD-1 could synergistically treat HCC progression. This study identified new treatment targets and strategies for HCC progression, contributing to patients with advanced HCC from new perspectives.
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