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

Minying Zhang, Jens Fritsche, Jason Roszik, Leila J. Williams, Xinxin Peng, Yulun Chiu, Chih-Chiang Tsou, Franziska Hoffgaard, Valentina Goldfinger, Oliver Schoor, Amjad Talukder, Marie A. Forget, Cara Haymaker, Chantale Bernatchez, Leng Han, Yiu-Huen Tsang, Kathleen Kong, Xiaoyan Xu, Kenneth L. Scott, Harpreet Singh-Jasuja, Greg Lizee, Han Liang, Toni Weinschenk (), Gordon B. Mills () and Patrick Hwu ()
Additional contact information
Minying Zhang: The University of Texas MD Anderson Cancer Center
Jens Fritsche: Immatics Biotechnologies
Jason Roszik: The University of Texas MD Anderson Cancer Center
Leila J. Williams: The University of Texas MD Anderson Cancer Center
Xinxin Peng: The University of Texas MD Anderson Cancer Center
Yulun Chiu: The University of Texas MD Anderson Cancer Center
Chih-Chiang Tsou: Immatics US
Franziska Hoffgaard: Immatics Biotechnologies
Valentina Goldfinger: Immatics Biotechnologies
Oliver Schoor: Immatics Biotechnologies
Amjad Talukder: The University of Texas MD Anderson Cancer Center
Marie A. Forget: The University of Texas MD Anderson Cancer Center
Cara Haymaker: The University of Texas MD Anderson Cancer Center
Chantale Bernatchez: The University of Texas MD Anderson Cancer Center
Leng Han: The University of Texas Health Science Center at Houston McGovern Medical School
Yiu-Huen Tsang: Baylor College of Medicine
Kathleen Kong: Baylor College of Medicine
Xiaoyan Xu: The University of Texas MD Anderson Cancer Center
Kenneth L. Scott: Baylor College of Medicine
Harpreet Singh-Jasuja: Immatics Biotechnologies
Greg Lizee: The University of Texas MD Anderson Cancer Center
Han Liang: The University of Texas MD Anderson Cancer Center
Toni Weinschenk: Immatics Biotechnologies
Gordon B. Mills: The University of Texas MD Anderson Cancer Center
Patrick Hwu: The University of Texas MD Anderson Cancer Center

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-06405-9

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