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.
Keywords: T-cells; acidosis; cancer; immunotherapy; metabolism; tumour microenvironment.
© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.