Unmask hidden antigens with a short epigenetic course before immunotherapy
Low doses of drugs that change how DNA is packaged can make cancer cells display more of what marks them as abnormal, potentially waking up immunotherapy in cold tumours.
Hypomethylating agents de-repress endogenous retroviruses and cancer-testis antigens and induce viral mimicry through interferon signalling, and HDAC or EZH2 inhibition can restore antigen presentation machinery. Trials combining epigenetic agents with checkpoint blockade in colorectal and lung cancer have been mostly small, with variable schedules and no pharmacodynamic gating. Dose and schedule, rather than the concept, are probably the reason for inconsistency.
- 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.
- Cold tumours and the immunosuppressive microenvironment · Most tumours keep the immune system out or asleep, so immunotherapy helps only a minority.
- Too many combinations to test · There are thousands of possible drug pairs and sequences. Trials can test a few dozen a year.
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not linked directly; found by shared links- PersonStephen B. Baylin
Shares Azacitidine, DNA methylation profiling, Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET), Non-small-cell lung cancer.
- TrialKEYNOTE-177
Shares Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Cold tumours and the immunosuppressive microenvironment, No one can predict who responds to immunotherapy, Immune checkpoint inhibitors.
- InstitutionUSC Norris Comprehensive Cancer Center
Shares Azacitidine, DNA methylation profiling, Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET), Colorectal cancer.
- IdeaReprogramme suppressive macrophages instead of trying to delete them
Shares Hot vs cold tumours, Cold tumours and the immunosuppressive microenvironment, No one can predict who responds to immunotherapy, Immune checkpoint inhibitors.
- IdeaMake every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours
Shares Hot vs cold tumours, Cold tumours and the immunosuppressive microenvironment, No one can predict who responds to immunotherapy, Immune checkpoint inhibitors.
- IdeaBlock the complement signal that recruits tumour-protecting cells
Shares Hot vs cold tumours, Cold tumours and the immunosuppressive microenvironment, Immune checkpoint inhibitors, Non-small-cell lung cancer.
- TrialMEVPRO-1
Shares Mevrometostat, EZH2.
- IdeaClear the suppressive neutrophils out of pancreatic tumours first
Shares Hot vs cold tumours, Cold tumours and the immunosuppressive microenvironment, No one can predict who responds to immunotherapy, Immune checkpoint inhibitors.