Abstract

High mutational load gets a response Cancers harbor many genetic mutations. Defects in DNA mismatch repair prevent tumors from repairing certain types of DNA damage and lead to a hypermutable genomic state known as microsatellite instability (MSI). Some tumors with a high degree of MSI may be treatable with PD-1 (programmed cell death–1) immunotherapy, but patient response is highly variable. Mandal et al. studied drivers of differential response to immunotherapy in these patients and found that MSI intensity and insertion-deletion mutations strongly affected therapeutic outcome. Science , this issue p. 485