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RNA editing derived epitopes function as cancer antigens to elicit immune responses.

Minying ZhangJens FritscheJason RoszikLeila J WilliamsXinxin PengYulun ChiuChih-Chiang TsouFranziska HoffgaardValentina GoldfingerOliver SchoorAmjad TalukderMarie A ForgetCara HaymakerChantale BernatchezLeng HanYiu-Huen TsangKathleen KongXiaoyan XuKenneth L ScottHarpreet Singh-JasujaGreg LizeeHan LiangToni WeinschenkGordon B MillsPatrick Hwu
Published in: Nature communications (2018)
In addition to genomic mutations, RNA editing is another major mechanism creating sequence variations in proteins by introducing nucleotide changes in mRNA sequences. Deregulated RNA editing contributes to different types of human diseases, including cancers. Here we report that peptides generated as a consequence of RNA editing are indeed naturally presented by human leukocyte antigen (HLA) molecules. We provide evidence that effector CD8+ T cells specific for edited peptides derived from cyclin I are present in human tumours and attack tumour cells that are presenting these epitopes. We show that subpopulations of cancer patients have increased peptide levels and that levels of edited RNA correlate with peptide copy numbers. These findings demonstrate that RNA editing extends the classes of HLA presented self-antigens and that these antigens can be recognised by the immune system.
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