TY - JOUR
T1 - Neoantigens in MDS Are Associated with Two Novel CD4+ T Cell Subsets and Improved Overall Survival
AU - Coats, Thomas
AU - Smith, Alexander E
AU - Mourikis, Athanasios
AU - Shahin, Tala
AU - Kulasekararaj, Austin G
AU - Best, Steve
AU - Chitre, Sneha
AU - Ellis, Richard
AU - Petrov, Nedyalko
AU - Heck, Susanne
AU - Irish, Jonathan M.
AU - Kordasti, Shahram
AU - Mufti, Ghulam J
PY - 2017
Y1 - 2017
N2 - 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
AB - 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
M3 - Article
VL - 130
SP - 2958
JO - Blood (ASH Annual Meeting Abstracts)
JF - Blood (ASH Annual Meeting Abstracts)
IS - Suppl 1
ER -