Related Experiment Video
Updated: May 16, 2025
Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts
Published on: September 1, 2018
Transcript-targeted antigen mapping reveals the potential of POSTN splicing junction epitopes in glioblastoma
Zujian Xiong1,2,3, Chaim T Sneiderman2, Chloe R Kuminkoski2
1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Abstract:
Tumor antigens are crucial for T-cell mediated immunotherapy, but identified antigens for gliomas remain limited. Aberrant splicing variants are commonly expressed in tumors, resulting in unique tumor isoforms with potential antigenic properties. Herein, we analyzed multi-omics data from 587 glioma patients and assembled a library of putative tumor-enriched isoform antigens (TIA) and corresponding peptides presented on each HLA-I allele. We constructed an individual-specific TIA peptide candidate repertoire for each patient based on their TIA expression and HLA-I haplotypes. TIAs were highly expressed, enriched with glioma malignancy, and demonstrated strong HLA-binding affinity. We focused on periostin isoform-203 (POSTN-203), which was associated with poor survival of patients and contained multiple predicted HLA-restricted peptide epitopes. A selected HLA-A11-restricted peptide from POSTN-203 (POSTN-203A11) induced antigen-specific T-cell responses against both peptide-pulsed and POSTN-203-expressing glioma cells in an HLA-specific manner. Our findings highlight TIAs as a promising source of immunogenic antigens and POSTN-203 as a potential promising target for glioma immunotherapy.
Insights
Tumor antigens are crucial for glioma immunotherapy. Researchers identified novel tumor-enriched isoform antigens (TIAs), including POSTN-203, which can elicit T-cell responses against glioma cells.
Area of Science:
- Oncology
- Immunology
- Bioinformatics
Background:
- Limited identified tumor antigens hinder effective glioma immunotherapy.
- Aberrant splicing in tumors creates unique tumor isoforms with antigenic potential.
Purpose of the Study:
- To identify and characterize novel tumor-enriched isoform antigens (TIAs) for glioma immunotherapy.
- To develop patient-specific TIA peptide repertoires for personalized treatment strategies.
Main Methods:
- Analysis of multi-omics data from 587 glioma patients.
- Assembly of a TIA library with corresponding HLA-I presented peptides.
- Construction of individual-specific TIA peptide candidate repertoires.
- Focus on periostin isoform-203 (POSTN-203) and its HLA-A11-restricted peptide (POSTN-203A11).
Main Results:
- TIAs were highly expressed, enriched in glioma malignancy, and showed strong HLA-binding affinity.
- POSTN-203 was associated with poor patient survival and contained multiple predicted HLA-restricted epitopes.
- POSTN-203A11 induced antigen-specific T-cell responses against POSTN-203-expressing glioma cells in an HLA-specific manner.
Conclusions:
- TIAs represent a promising source of immunogenic antigens for cancer immunotherapy.
- POSTN-203 and its derived peptides are potential therapeutic targets for glioma immunotherapy.
