Identification and ranking of recurrent neo-epitopes in cancer

• Published in: BMC medical genomics Vol. 12; no. 1; p. 171
• Main Authors: Blanc, Eric, Holtgrewe, Manuel, Dhamodaran, Arunraj, Messerschmidt, Clemens, Willimsky, Gerald, Blankenstein, Thomas, Beule, Dieter
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 27.11.2019; BioMed Central; BMC
• Subjects: Algorithms; Alleles; Amino acids; Animals; Antigen presentation; Antigenic determinants; Antigens; Artificial intelligence; Bioinformatics; Cancer; Cancer cells; Cancer immunotherapy; Cancer treatment; Candidates; Computational Biology - methods; Databases, Factual; Epitopes; Epitopes - genetics; Epitopes - immunology; Genes, MHC Class I - genetics; Genomes; Histocompatibility antigen HLA; Humans; Immune system; Immunotherapy; Lymphocytes; Lymphocytes T; Machine learning; Major histocompatibility complex; Mice; Mutation; Neo-antigen; Neo-epitope; Neoplasms - genetics; Neoplasms - immunology; Patients; Peptides; Precision treatment; Proteins; Rankings; Recurrence (Disease); Studies; T cells; Neo-epitope; Precision treatment; Immunotherapy; Neo-antigen; Cancer
• ISSN: 1755-8794; 1755-8794
• DOI: 10.1186/s12920-019-0611-7

Immune escape is one of the hallmarks of cancer and several new treatment approaches attempt to modulate and restore the immune system's capability to target cancer cells. At the heart of the immune recognition process lies antigen presentation from somatic mutations. These neo-epitopes are emerging as attractive targets for cancer immunotherapy and new strategies for rapid identification of relevant candidates have become a priority. We carefully screen TCGA data sets for recurrent somatic amino acid exchanges and apply MHC class I binding predictions. We propose a method for in silico selection and prioritization of candidates which have a high potential for neo-antigen generation and are likely to appear in multiple patients. While the percentage of patients carrying a specific neo-epitope and HLA-type combination is relatively small, the sheer number of new patients leads to surprisingly high reoccurence numbers. We identify 769 epitopes which are expected to occur in 77629 patients per year. While our candidate list will definitely contain false positives, the results provide an objective order for wet-lab testing of reusable neo-epitopes. Thus recurrent neo-epitopes may be suitable to supplement existing personalized T cell treatment approaches with precision treatment options.