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-JasujaGreg Lizee, Han Liang, Toni Weinschenk, Gordon B. Mills, Patrick Hwu

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Article number3919
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Zhang, M., Fritsche, J., Roszik, J., Williams, L. J., Peng, X., Chiu, Y., Tsou, C. C., Hoffgaard, F., Goldfinger, V., Schoor, O., Talukder, A., Forget, M. A., Haymaker, C., Bernatchez, C., Han, L., Tsang, Y. H., Kong, K., Xu, X., Scott, K. L., ... Hwu, P. (2018). RNA editing derived epitopes function as cancer antigens to elicit immune responses. Nature communications, 9(1), [3919]. https://doi.org/10.1038/s41467-018-06405-9