Integrating spatial omics and single- cell mass spectrometry imaging reveals tumor-host metabolic interplay in hepatocellular carcinoma

• 成果类型: Article
• 署名作者: Chen, Panpan; Geng, Haoyuan; Ma, Bangzhen; Zhang, Yaqi; Zhu, Zihan; Li, Min; Chen, Shiping; Wang, Xiao; Sun, Chenglong
• 署名单位: Qilu University of Technology; Qilu University of Technology; Shandong First Medical University & Shandong Academy of Medical Sciences
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15235
• DOI: 10.1073/pnas.2505789122
• 发表日期: 2025-08-05
• 关键词: cancer; microenvironment; proteomics; expression

摘要

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.