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Potential shared neoantigens from pan-cancer transcript isoforms

Jirapat Techachakrit1,2, Aijaz Ahmad Malik1, Trairak Pisitkun2,3

  • 1Center of Excellence in Computational Molecular Biology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.

Scientific Reports
|May 7, 2025
PubMed

Insights

Cancer isoform switching creates shared neoantigens, offering a promising avenue for broad immunotherapies applicable to many patients, reducing the need for personalized cancer treatments.

Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Isoform switching is common in cancer and can generate unique cancer-specific proteins.
  • These proteins may serve as neoantigens, potentially eliciting an immune response.
  • Current immunotherapies often rely on personalized neoantigen identification.

Purpose of the Study:

  • To identify common cancer-associated isoform switching events across multiple cancer types.
  • To investigate the potential of these events as a source of broadly applicable neoantigens for immunotherapy.
  • To assess the immunogenicity of neoantigens derived from isoform switching.

Main Methods:

  • Integrated five large-scale transcriptomic datasets (>19,500 samples, 29 cancer types).
  • Identified cancer-associated isoform switching events.
  • Confirmed neoantigen-containing peptides in proteome datasets.
  • Performed molecular dynamics simulations to predict neoantigen-HLA binding affinity.

Main Results:

  • Identified common isoform switching events in multiple cancer types, some involving oncogenic genes.
  • Confirmed the presence of neoantigen-containing peptides from these events in proteomic data.
  • Demonstrated predicted binding affinity of neoantigens to the human leukocyte antigen (HLA) complex.
  • Provided strong evidence for isoform switching as a source of actionable neoantigens.

Conclusions:

  • Cancer-associated isoform switching is a significant source of actionable neoantigens.
  • These neoantigens have the potential to trigger an immune response.
  • Isoform switching events could be leveraged for broad, non-personalized immunotherapeutic strategies across various cancer types.
Keywords:
Immunotherapy targetsIsoform switchingShared pan-cancer neoantigens

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