Abstract Cancer cells accumulate somatic mutations that can give rise to novel amino acid sequences absent from the normal human proteome. These mutation-derived, cancer-specific peptides are referred to as “neo-peptides.” A subset of neo-peptides capable of eliciting an immune response are termed “neo-epitopes.” Neo-epitopes hold significant promise for precision cancer immunotherapy, both as therapeutic targets and as biomarkers for prognosis and treatment response. Given their central role in immuno-oncology, we performed a meta-analysis to systematically assess how experimental evidence shapes current understanding of neo-epitope biology. Our study is the largest reported to date. Using the Cancer Epitope Database and Analysis Resource (CEDAR), we analyzed over 16,000 neo-peptides tested in more than 20,000 T cell assays across 180 studies. We analyzed frequently utilized assay types, the genes neo- epitopes are derived from, and their driver gene status, variations across cancer types, mutation patterns and their physicochemical properties, HLA restrictions, and predicted MHC binding. We found that validated neo-epitope frequencies varied across cancer types, with the highest rates in skin and lung and the lowest in colorectal cancer. Neo-epitopes were enriched in driver genes such as TP53 and KRAS. However, testing frequency correlated with mutation prevalence, revealing a bias toward recurrent mutations. Despite the high sequence similarity among RAS family members, validated neo-epitope overlap was minimal, challenging pan-RAS strategies. Shared neo-epitopes across cancer types are rare, with only 16 validated in more than one cancer type. While most assays involved HLA class I, class II alleles presented a higher proportion of validated neo-epitopes. Specific alleles, including HLA-B*40:01 and HLA- DRB1*11:01, were enriched for presenting neo-epitopes, whereas others, like HLA-A*02:01, were enriched for presenting neo-peptides that are not recognized by T cells. Finally, amino acid substitutions that altered hydrophobicity or charge were more common in neo-epitopes. Citation Format: Zeynep Kosaloglu-Yalcin, Ibel Carri, Bjoern Peters, Alessandro Sette. Meta-Analysis of Neoantigens: Insights from the Cancer Epitope Database and Analysis Resource (CEDAR) abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr PR-09.
Koşaloğlu et al. (Wed,) studied this question.