Cancer Research UK Beatson Institute, Glasgow, UK.
School of Cancer Sciences, University of Glasgow, UK.
Mol Oncol. 2023 Apr;17(4):541-544. doi: 10.1002/1878-0261.13400. Epub 2023 Mar 4.
Bicarbonate transport is a pre-existing mechanism of pH regulation in pancreatic ductal cells. In a recent study, Cappellesso et al. demonstrated that pancreatic ductal adenocarcinoma metabolic rewiring creates an acidic environment, enhanced by bicarbonate import into cancer cells via SLC4A4. This acidity favours protumourigenic immunosuppression. Targeting SLC4A4 neutralises environmental pH and restores antitumour immunity, sensitising tumours to immune checkpoint blockade.
碳酸氢盐转运是胰腺导管细胞中 pH 调节的一种预先存在的机制。在最近的一项研究中,Cappellesso 等人证明,胰腺导管腺癌的代谢重编程产生了酸性环境,通过 SLC4A4 将碳酸氢盐导入癌细胞进一步增强了酸性环境。这种酸度有利于促进肿瘤发生的免疫抑制。靶向 SLC4A4 可使环境 pH 值中和并恢复抗肿瘤免疫,使肿瘤对免疫检查点阻断更加敏感。