Abstract 688: Pan-cancer mapping of genetic immune escape evolutionary trajectories.

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Abstract 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 IFNγ 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. Citation Format: Shengqing Gu, Wenjie Chen, Toby Baker, Zhihui Zhang, Huw A. Ogilvie, Peter Van Loo. Pan-cancer mapping of genetic immune escape evolutionary trajectories [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 688.

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