{"entity":{"id":"idea-bio2-lactate-acid-axis","kind":"idea","name":"De-acidify the tumour so T cells can work in it","aka":[],"tldr":"Tumours are acidic, and immune cells stop working in acid. Neutralising that acid, or blocking the pumps that create it, might let immunotherapy work.","summary":"Tumour lactate export via MCT1 and MCT4 acidifies the microenvironment and directly impairs T-cell and natural killer cell function, while feeding regulatory T cells. Oral buffer therapy reversed acid-mediated immune exclusion in mouse models, and MCT1 inhibitors have been in early clinical trials. Nobody has tested pH modulation with a pH-imaging readout in patients receiving checkpoint blockade.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["pancreatic","melanoma"],"sections":[],"technologies":["checkpoint-inhibitor","mri","fdg-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cold-vs-hot","suv"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Raising intratumoural pH, measured by a validated imaging or biopsy method, increases intratumoural T-cell function markers and improves checkpoint blockade response in acidic, glycolysis-high tumours.","rationale":"Acid inhibition of T cells is well replicated in vitro and in mice, and pH is a tractable, measurable and potentially drug-independent variable. Selecting patients by tumour acidity is the missing step, and MRI and PET methods for tumour pH exist in research settings.","test":"A window-of-opportunity trial combining an approved checkpoint inhibitor with buffer therapy or an MCT inhibitor in glycolysis-high tumours, with pH imaging and paired biopsies as primary endpoints.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":8},"route":"/ideas/idea-bio2-lactate-acid-axis/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"}],"term":[{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"suv","kind":"term","name":"Standardised uptake value (SUV)","route":"/terms/suv/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"paper":[{"id":"paper-haslam-jama-netw-open","kind":"paper","name":"Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs","route":"/key-papers/paper-haslam-jama-netw-open/"}]}}