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Updated: Aug 11, 2025

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

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Epigenetically controlled tumor antigens derived from splice junctions between exons and transposable elements

Marianne Burbage1, Ares Rocañín-Arjó1, Blandine Baudon1

  • 1Institut Curie, Université Paris Sciences et Lettres, 75005 Paris, France.

Science Immunology
|February 3, 2023
PubMed

Insights

New tumor antigens arise from splicing between exons and transposable elements (TEs). These exon-TE junctions are immunogenic and can be targeted for cancer vaccines, showing promise for cancer therapy.

Area of Science:

  • Oncology
  • Immunology
  • Epigenetics

Background:

  • Epigenetic alterations, including transposable element (TE) derepression and alternative splicing defects, are common in cancer.
  • Noncanonical splice junctions between exons and TEs are potential sources of tumor-specific antigens.

Purpose of the Study:

  • To investigate exon-TE splicing junctions as a source of tumor-specific antigens.
  • To assess the immunogenicity and therapeutic potential of peptides derived from these junctions.

Main Methods:

  • Analysis of mRNA junctions in normal and tumor tissues.
  • Immunopeptidome profiling of tumor cell lines.
  • In vivo vaccination studies in tumor-bearing mice.
  • Investigation of the role of Setdb1 in regulating exon-TE junctions.

Main Results:

  • Exon-TE splicing junctions are expressed in normal tissues and tumors, with some being tumor-specific.
  • Peptides derived from exon-TE junctions were identified on MHC-I molecules in tumor cells.
  • These peptides elicited immunogenic responses in mice and delayed tumor growth upon vaccination.
  • Inactivation of Setdb1 led to increased expression of immunogenic exon-TE junctions.

Conclusions:

  • Exon-TE splicing junctions represent epigenetically regulated, immunogenic tumor antigens in mice.
  • These findings open new avenues for tumor targeting and cancer vaccination strategies.

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