Five dominant amino acid substitution signatures shape tumour immunity (opens in new tab)

Although numerous mutational processes operate in cancer, their functional impacts are unclear. We hypothesised that certain mutation sources preferentially generate amino acid substitutions that evade immune recognition, producing immune-cold tumours regardless of tissue or mutation load. By analysing 9300 cancer exomes and performing mutagenesis experiments, we mapped links between mutagens, DNA-repair defects, and amino acid substitution signatures (AAS). Surprisingly, the spectrum collaps...