Reprogramme suppressive macrophages instead of trying to delete them
Tumours fill with immune cells that protect them. Earlier drugs tried to remove those cells and failed. Newer ones aim to switch them to the attacking side.
CSF1R inhibitors depleted macrophages broadly and produced little benefit outside tenosynovial giant cell tumour, plausibly because depletion removes useful cells alongside harmful ones. TREM2, MARCO and LILRB2 mark specific suppressive macrophage states in human tumour single-cell atlases, and antibodies against them are in early trials. The proposition is state-switching, verified by on-treatment biopsies, rather than depletion.
- 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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Shares Hot vs cold tumours, Cold tumours and the immunosuppressive microenvironment, Immune checkpoint inhibitors, Colorectal cancer.