Check whether a tumour can still show itself to the immune system
Some tumours have broken the machinery that displays their identity to immune cells. Those patients cannot benefit from most immunotherapy and should be routed elsewhere.
Loss of HLA heterozygosity, B2M mutation, JAK1/2 loss and antigen presentation machinery defects are recurrent mechanisms of primary and acquired checkpoint resistance, and each is detectable from sequencing of tumour and germline. Routine reporting of an antigen presentation integrity score would identify patients who should be routed to HLA-independent therapies such as antibody-drug conjugates, natural killer cell engagers or CAR products.
- 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.
- Acquired resistance to every therapy · Nearly every targeted therapy stops working within months to a few years as the tumour adapts.
- Biomarkers are not validated or standardised · Tests that decide who gets a drug are often not validated prospectively and are measured differently in every lab.
Pages like this
not linked directly; found by shared links- Key paperGerlinger: a single biopsy misses most of the mutations in a kidney tumour
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- IdeaTreat resistance like an infectious disease and run national surveillance
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- IdeaA standard evolvability score for every tumour
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- InstitutionLeiden University Medical Center
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