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

Author

Listed:
  • 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
    China Medical University)

  • Kenneth L. Scott

    (Baylor College of Medicine)

  • Harpreet Singh-Jasuja

    (Immatics Biotechnologies
    Immatics US)

  • Greg Lizee

    (The University of Texas MD Anderson Cancer Center)

  • Han Liang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Toni Weinschenk

    (Immatics Biotechnologies
    Immatics US)

  • Gordon B. Mills

    (The University of Texas MD Anderson Cancer Center)

  • Patrick Hwu

    (The University of Texas MD Anderson Cancer Center)

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.

Suggested Citation

  • 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. , 2018. "RNA editing derived epitopes function as cancer antigens to elicit immune responses," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06405-9
    DOI: 10.1038/s41467-018-06405-9
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    Cited by:

    1. Celina Tretter & Niklas Andrade Krätzig & Matteo Pecoraro & Sebastian Lange & Philipp Seifert & Clara Frankenberg & Johannes Untch & Gabriela Zuleger & Mathias Wilhelm & Daniel P. Zolg & Florian S. Dr, 2023. "Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. Wojciech Barczak & Simon M. Carr & Geng Liu & Shonagh Munro & Annalisa Nicastri & Lian Ni Lee & Claire Hutchings & Nicola Ternette & Paul Klenerman & Alexander Kanapin & Anastasia Samsonova & Nicholas, 2023. "Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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