Pan-cancer mapping of genetic immune escape evolutionary trajectories

Immune escape is a fundamental hallmark of cancer, facilitating disease progression and resistance to therapy. The temporal dynamics and genetic evolution underlying immune escape across diverse cancers remain incompletely characterized. Here we developed an integrative framework that systematically identifies immunomodulatory genes from functional genomic screens and reconstructs tumor evolutionary history using whole-genome sequencing data to infer mutation timing. Applying this approach to 2,658 tumors across 38 cancer types, we generated the first pan-cancer atlas of immune escape evolution, revealing distinct trajectories such as late amino acid metabolism mutations in pancreatic adenocarcinoma, early neuroactive ligand-receptor and IFNgamma pathway mutations in esophageal adenocarcinoma, and late protein methylation mutations in breast adenocarcinoma. These findings provide a comprehensive map of genetic immune evasion evolution, offering insights that may inform early detection strategies, immunoprevention, and therapeutic interventions across cancers. To facilitate easy access to the results, we further built a user-friendly website to interactively interrogate the evolution of immune escape.