包括结直肠癌 (CRC) 在内的多种癌症在肥胖人群中更为常见，而且往往更具侵袭性。在这里，我们发现巨噬细胞在肥胖和结直肠癌患者以及肥胖结直肠癌小鼠的肿瘤内积累，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衍生的酸产生引发的，并由巨噬细胞通过酸敏感受体 GPR65 发出的信号驱动。我们发现 GPR65 在肥胖小鼠的肝细胞癌 (HCC) 中具有类似的作用。肥胖和结直肠癌或肝癌患者的肿瘤也表现出 GPR65 表达增加，这表明本文揭示的机制可能有助于一系列肥胖相关癌症的肿瘤生长，并代表了潜在的治疗靶点。

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.