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ISOTOPE: ISOform-guided prediction of epiTOPEs in cancer

Juan L Trincado1, Marina Reixachs-Solé2,3, Judith Pérez-Granado4

  • 1Josep Carreras Leukemia Research Institute, Badalona, Spain.

Plos Computational Biology
|September 16, 2021
PubMed

Insights

Identifying tumor-specific splicing events can reveal new targets for cancer immunotherapy. Our pipeline, ISOTOPE, finds these splicing-derived neoepitopes, with higher MHC-I binding affinity linked to better therapy response.

Area of Science:

  • Oncology
  • Immunology
  • Bioinformatics

Background:

  • Immunotherapies offer effective treatments for various cancers.
  • Identifying tumor-specific epitopes is crucial for understanding therapy response.
  • Splicing alterations in tumors can generate novel epitopes.

Purpose of the Study:

  • To introduce ISOTOPE, a pipeline for identifying tumor-specific splicing-derived epitopes.
  • To analyze the role of splicing alterations in generating neoepitopes.
  • To investigate the association between splicing-derived neoepitopes and immunotherapy response.

Main Methods:

  • Development of the ISOTOPE (ISOform-guided prediction of epiTOPEs In Cancer) pipeline.
  • Utilizing RNA sequencing and mass spectrometry to identify MHC-I associated proteins.
  • Analysis of tumor samples to compare splicing alterations and somatic mutations.

Main Results:

  • ISOTOPE identified neoepitopes from tumor-specific splicing events.
  • Splicing alterations can generate more candidate neoepitopes than somatic mutations.
  • Higher MHC-I binding affinity of splicing-derived neoepitopes correlated with positive immunotherapy response.

Conclusions:

  • Tumor-specific splicing alterations contribute to epitope diversity and immunogenicity.
  • Studying splicing alterations is essential for comprehensive tumor characterization in immunotherapy.
  • ISOTOPE provides a valuable tool for discovering novel neoepitopes from splicing events.

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