肿瘤巨噬细胞上的酸感应受体 GPR65 推动肥胖症肿瘤的生长

IF 17.6 1区医学 Q1 IMMUNOLOGY Science Immunology Pub Date : 2024-10-18 DOI:10.1126/sciimmunol.adg6453

Sreya Bagchi, Robert Yuan, Han-Li Huang, Weiruo Zhang, David Kung-Chun Chiu, Hyungjoo Kim, Sophia L. Cha, Lorna Tolentino, Joshua Lowitz, Yilin Liu, Anna Moshnikova, Oleg Andreev, Sylvia Plevritis, Edgar G. Engleman

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摘要

包括结肠直肠癌（CRC）在内的多种癌症在肥胖患者中的发病率更高，而且往往更具侵袭性。在这里，我们发现巨噬细胞在肥胖症和 CRC 患者的肿瘤内以及肥胖 CRC 小鼠体内聚集，并促进肿瘤加速生长。这些变化是由油酸积累和随后肿瘤细胞产生的酸引起的，并且是由巨噬细胞通过酸感应受体 GPR65 发出信号驱动的。我们发现 GPR65 在肥胖小鼠肝细胞癌（HCC）中也起着类似的作用。肥胖和 CRC 或 HCC 患者的肿瘤也表现出 GPR65 表达的增加，这表明本文揭示的机制可能导致一系列肥胖相关癌症的肿瘤生长，并成为潜在的治疗靶点。

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The acid-sensing receptor GPR65 on tumor macrophages drives tumor growth in obesity

Multiple cancers, including colorectal cancer (CRC), are more frequent and often more aggressive in individuals with obesity. Here, we showed that macrophages accumulated within tumors of patients with obesity and CRC and in obese CRC mice and that they promoted accelerated tumor growth. These changes were initiated by oleic acid accumulation and subsequent tumor cell–derived acid production and were driven by macrophage signaling through the acid-sensing receptor GPR65. We found a similar role for GPR65 in hepatocellular carcinoma (HCC) in obese mice. Tumors in patients with obesity and CRC or HCC also exhibited increased GPR65 expression, suggesting that the mechanism revealed here may contribute to tumor growth in a range of obesity-associated cancers and represent a potential therapeutic target.

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来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.