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Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response

Author

Listed:
  • Wojciech Barczak

    (University of Oxford)

  • Simon M. Carr

    (University of Oxford)

  • Geng Liu

    (University of Oxford)

  • Shonagh Munro

    (Argonaut Therapeutics Ltd, Oxford Science Park)

  • Annalisa Nicastri

    (University of Oxford)

  • Lian Ni Lee

    (University of Oxford)

  • Claire Hutchings

    (University of Oxford)

  • Nicola Ternette

    (University of Oxford)

  • Paul Klenerman

    (University of Oxford)

  • Alexander Kanapin

    (Peter the Great Saint Petersburg Polytechnic University)

  • Anastasia Samsonova

    (Peter the Great Saint Petersburg Polytechnic University)

  • Nicholas B. Thangue

    (University of Oxford)

Abstract

Protein arginine methyltransferase (PRMT) 5 is over-expressed in a variety of cancers and the master transcription regulator E2F1 is an important methylation target. We have explored the role of PRMT5 and E2F1 in regulating the non-coding genome and report here a striking effect on long non-coding (lnc) RNA gene expression. Moreover, many MHC class I protein-associated peptides were derived from small open reading frames in the lncRNA genes. Pharmacological inhibition of PRMT5 or adjusting E2F1 levels qualitatively altered the repertoire of lncRNA-derived peptide antigens displayed by tumour cells. When presented to the immune system as either ex vivo-loaded dendritic cells or expressed from a viral vector, lncRNA-derived peptides drove a potent antigen-specific CD8 T lymphocyte response, which translated into a significant delay in tumour growth. Thus, lncRNA genes encode immunogenic peptides that can be deployed as a cancer vaccine.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36826-0
    DOI: 10.1038/s41467-023-36826-0
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