Abstract
BackgroundImmune 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.MethodsWe carefully screen TCGA data sets for recurrent somatic amino acid exchanges and apply MHC class I binding predictions.ResultsWe 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.ConclusionWhile 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.
Highlights
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
1,055 variants are deemed recurrent (Additional file 1), as they can be found in more than 1% of the patients in the respective study cohort. These recurrent variants correspond to 869 unique protein changes, as some appear in multiple cancer entities. 77 of the recurrent variants occur in at least 3% of their cohort (43 unique protein changes). From these 869 unique protein changes, we have generated candidates that are predicted to be strong MHC class I binders in frequent HLA-1 types that we considered for initial selection. 415 (48%) of them lead to a strong binder prediction
Using existing cancer studies and neo-epitope binding predictions to MHC class I proteins, we propose a ranking of candidates which mutation occur frequently in observed cancer patient cohorts
Summary
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. While not yet fully understood, immune response and recognition of tumor cells containing specific peptides depends critically on the ability of the MHC class I complexes to bind to the peptide in order to present it to a T cell. With the advent of affordable short read sequencing, comprehensive neo-antigen screening based on whole exome sequencing has become feasible and many cancer immune therapeutic approaches try to utilize detailed understanding of the neo-epitope spectrum to create additional or boost pre-existing T cell reactivity for therapeutic purposes [8, 9]. We search and prioritize neo-epitope candidates which have a high potential for neo-antigen generation and are likely to appear in multiple
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