Pick the radiation dose that switches the immune alarm on, not off
Radiation can alert the immune system, but too big a single dose destroys the very alarm signal it creates. Picking the right dose and schedule may be free extra benefit.
Single fractions above roughly 12-18 Gy induce the DNA exonuclease TREX1, which degrades cytoplasmic DNA and prevents cGAS-STING activation, whereas fractionated schedules around 8 Gy times three maximise interferon signalling in mouse models. Radiotherapy plus immunotherapy trials have used dose and fractionation chosen for tumour control or convenience, not for immune priming, which may explain inconsistent abscopal results.
- Cold tumours and the immunosuppressive microenvironment · Most tumours keep the immune system out or asleep, so immunotherapy helps only a minority.
- Surgery and radiotherapy cure most, get least · Surgery and radiotherapy cure more people than drugs do, but attract a fraction of the research investment.
- 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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