FABP5

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Tác giả: Bo Deng, Wenxue Feng, Jingyan Gu, Yangyang Guo, Chencheng Hu, Xiaoqian Hu, Xiaowu Huang, Jia Li, Yuli Lin, Sheng Su, Yaqi Wan, Zhihao Wu, Yanyong Xu, Xuguang Yang, Weiwei Zhao

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Netherlands : Journal of hepatology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 715420

BACKGROUND & AIMS: Tumour-associated macrophages (TAMs) contribute to hepatocellular carcinoma (HCC) progression. However, while the pro-tumour and immunosuppressive roles of lipid-loaded macrophages are well established, the mechanisms by which lipid metabolism enhances the tumour-promoting effects of TAMs remain unclear. METHODS: Single-cell RNA sequencing was performed on mouse and human HCC tumour samples to elucidate the landscape of HCC TAMs. Macrophages were stimulated with various long-chain unsaturated fatty acids (UFAs) to assess immunosuppressive molecule expression in vitro. Additionally, in vivo and in vitro studies were conducted using mice with macrophage-specific deficiencies in fatty acid-binding protein 5 (FABP5) or peroxisome proliferator-activated receptor γ (PPARγ). RESULTS: Single-cell RNA sequencing identified a subpopulation of FABP5 CONCLUSIONS: This study demonstrates that UFAs promote tumourigenesis by enhancing the immunosuppressive tumour microenvironment via FABP5-PPARγ signalling and provides a proof-of-concept for targeting this pathway to improve the efficacy of tumour immunotherapy. IMPACT AND IMPLICATIONS: Despite the role of tumour-associated macrophages (TAMs) in promoting tumour progression being well established, the mechanisms by which lipid metabolism enhances the tumour-promoting effects of TAMs remain unclear. Our study reveals that FABP5-mediated unsaturated fatty acid metabolism in TAMs is crucial for modulating antitumour T-cell immunity and influencing the efficacy of immunotherapy. This finding provides novel insights into the immunomodulatory roles of FABP5
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