ArticleProceedings of the National Academy of Sciences of the United States of America2025
Integrating spatial omics and single-cell mass spectrometry imaging reveals tumor-host metabolic interplay in hepatocellular carcinoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Metabolomics and metabolites in cancer diagnosis and treatment.Molecular biomedicine · 2025Pooled it
- Unraveling the tapestry: Lessons from multi-omics and spatial biology in hepatocellular cancer.Hepatology (Baltimore, Md.) · 2026Review
- Cell-cycle reactivation and hepatocyte identity loss in hepatocellular carcinoma: Transcriptomic hallmarks and validation strategies (Review).Oncology letters · 2026Review
- Insights From Spatiality: Accelerating Pharmaceutical Research Using Mass Spectrometry Imaging.Medicinal research reviews · 2026Review
- Single-cell and spatial transcriptomics reveal lactate-active epithelial-immune cell crosstalk that reprograms the immune microenvironment in colorectal cancer.Translational oncology · 2026Article
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
- HNRNPU K181 Lactylation Drives Cervical Cancer Growth by Upregulating PHGDH and Reprogramming Serine Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Tumor microenvironment-specific nanomedicine: from biology-driven to multi-omics-guided precision engineering.Journal of hematology & oncology · 2026Review
- Advanced technologies of single-cell metabolomics unveiling cellular metabolic heterogeneity for biological and biomedical research.Journal of food and drug analysis · 2026Review
- The role of tumor metabolic reprogramming in acquired anti-PD-1/PD-L1 resistance.Translational lung cancer research · 2026Review
- Bidirectional crosstalk between cancer-associated fibroblasts and tumor immunity: shaping the microenvironment and response to immune checkpoint therapy.Experimental hematology & oncology · 2026Review
- Artificial Intelligence for Spatial Immunometabolic Analysis of the Tumor Microenvironment: Current Evidence and Future Directions.Current issues in molecular biology · 2026Review
- Review
- Advances in artificial metabzymes for macrophage polarization in tumor metabolic immunotherapy.Materials today. Bio · 2026Article
- Pleiotropic mechanisms of cancer-associated fibroblast-mediated resistance in hepatocellular carcinoma: emerging therapeutic vulnerabilities and targeting strategies.Cancer gene therapy · 2026Review
- AFP confers the resistance of lenvatinib in hepatocellular carcinoma by activating PI3K/AKT/LDHA signaling axis.Discover oncology · 2026Article
- Lactate-lactylation in tumor angiogenesis and progression: mechanisms, biomarker potential, and therapeutic implications.Biomarker research · 2026Review
- Lactic Acid in Tumour Biology.Metabolites · 2026Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Metabolic crosstalk among diverse cellular populations contributes to shaping a competitive and symbiotic tumor microenvironment (TME) to influence cancer progression and immune responses, highlighting vulnerabilities that can be exploited for cancer therapy. Using a spatial multiomics platform to study the cell-specific metabolic spectrum in hepatocellular carcinoma (HCC), we map the metabolic interactions between different cells in the HCC TME and identify a unique tumor-immune-cancer-associated fibroblast (CAF) "interface" zone, where cell-cell interactions are enhanced and accompanied by significant upregulation of lactic acid and long-chain polyunsaturated fatty acids. Further combining single-cell mass spectrometry imaging of patient-derived tumor organoids, cocultured CAFs, and macrophages, we demonstrate that CAFs increase glycolysis and secrete lactic acid to the surrounding microenvironment to drive immunosuppressive macrophage M2 polarization. These findings facilitate the understanding of cancer-associated metabolic interactions in complex TME and provide clues for targeted clinical therapies.
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Registered trials
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