# De-acidify the tumour so T cells can work in it

Source: https://onco.cc/ideas/idea-bio2-lactate-acid-axis/  
OnCo record `idea-bio2-lactate-acid-axis` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- 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): https://doi.org/10.1001/jamanetworkopen.2019.2535

## Connected records

- cancers: [Melanoma](https://onco.cc/cancers/melanoma/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [FDG PET](https://onco.cc/technologies/fdg-pet/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [MRI](https://onco.cc/technologies/mri/)
- terms: [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Standardised uptake value (SUV)](https://onco.cc/terms/suv/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/)
- key papers: [Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs](https://onco.cc/key-papers/paper-haslam-jama-netw-open/)

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