Neoantigens in MDS Are Associated with Two Novel CD4+ T Cell Subsets and Improved Overall Survival

Thomas Coats, Alexander E Smith, Athanasios Mourikis, Tala Shahin, Austin G Kulasekararaj, Steve Best, Sneha Chitre, Richard Ellis, Nedyalko Petrov, Susanne Heck, Jonathan M. Irish, Shahram Kordasti, Ghulam J Mufti

Research output: Contribution to journalArticlepeer-review

Abstract

Background The immune system has been shown to be important in the pathophysiology of MDS. Adaptive immunity relies on T cells ability to discriminate between self and non-self antigens in the context of a surface bound MHC protein structure. Genomic changes occurring in acquired somatic mutations can encode novel amino acid sequences, which if translated and presented by the MHC are termed a neoantigen. To establish the impact of neoantigens in MDS we have combined a predictive algorithm to screen cases for the presence of neoantigens together with mass cytometry by time of flight (CyTOF) to identify neoantigen-related immune signatures. Results Mutation screening was performed on 204 MDS patients using our established gene panel targeting mutations commonly occurring in MDS (Mohemdali, Leukaemia 2015). Neoantigen-MHC affinity was predicted using NetMHCpan3.0 with neoantigen affinities ranked against 400,000 naturally occurring peptides. Those in the top 2% of peptides were classed as predicted neoantigens. In a multi-variate analysis of overall survival, higher numbers of mutations were associated with a poorer outcome (HR 2.71 95%CI 1.28-5.73, p
Original languageEnglish
Pages (from-to)2958
Number of pages1
JournalBlood (ASH Annual Meeting Abstracts)
Volume130
Issue numberSuppl 1
Publication statusPublished - 2017

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