Make every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours
Immunotherapy works in tumours that immune cells can enter and ignores those that shut them out. Systematically test ways to open up the shut-out tumours, measured with spatial maps.
Most pancreatic, prostate, colorectal (microsatellite-stable), ovarian and glioma tumours are immune-excluded or immune-desert. Candidate strategies include stromal modulation (FAP, TGF-beta, CXCR4 antagonists), innate agonists (STING, TLR), oncolytic viruses, radiotherapy priming, and myeloid reprogramming (CD47, CSF1R). Each has been tested piecemeal. The proposal is a coordinated programme with standardised spatial immune profiling before and after each intervention in window-of-opportunity trials, a shared classification of exclusion mechanisms, and adaptive combination trials that match the mechanism of exclusion to the reprogramming strategy.
- Cold tumours and the immunosuppressive microenvironment · Most tumours keep the immune system out or asleep, so immunotherapy helps only a minority.
- No one can predict who responds to immunotherapy · Checkpoint drugs cure some patients and do nothing for most. We still cannot tell the two apart before treating.
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