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

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Protein arginine methyltransferase (PRMT) 5 is over-expressed in various cancers.
• PRMT5 targets the transcription regulator E2F1, influencing gene expression.
• The role of PRMT5 and E2F1 in non-coding genome regulation, particularly long non-coding (lnc) RNAs, is under investigation.

Purpose of the Study:

• To investigate the impact of PRMT5 and E2F1 on lncRNA gene expression.
• To explore the potential of lncRNA-derived peptides as cancer antigens.
• To assess the immunogenicity and anti-tumour efficacy of these peptides for cancer vaccine development.

Main Methods:

• Studied the effect of PRMT5 inhibition and E2F1 level modulation on lncRNA expression.
• Analyzed peptides derived from lncRNA genes presented by MHC class I molecules.
• Evaluated antigen-specific CD8 T lymphocyte responses to lncRNA-derived peptides using ex vivo dendritic cells and viral vectors.

Main Results:

• PRMT5 and E2F1 significantly affect lncRNA gene expression.
• Many MHC class I-associated peptides originate from small open reading frames within lncRNA genes.
• lncRNA-derived peptides elicit a potent CD8 T cell response, delaying tumor growth in vivo.

Conclusions:

• lncRNA genes encode immunogenic peptides.
• Modulating PRMT5 or E2F1 alters the landscape of lncRNA-derived peptide antigens.
• lncRNA-derived peptides represent a promising strategy for developing novel cancer vaccines.