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Updated: Aug 24, 2026
Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
AIM-2: a novel tumor antigen is expressed and presented by human glioma cells
Gentao Liu1, John S Yu, Gang Zeng
1Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. liug@cshs.org
Abstract:
Antigen isolated from Immunoselected Melanoma-2 (AIM-2) was recently identified using melanoma-reactive CD8 T cells. AIM-2 antigen is expressed in a wide variety of tumor types, including neuroectodermal tumors, as well as breast, ovarian and colon carcinomas. In this study, we analyzed AIM-2 expression in glioblastoma multiforme (GBM) in primary cultured cells and established GBM cell lines. We found that the primary GBM cell lines expressed 88.4% and 93.0% of non-spliced and spliced AIM-2, respectively. Five out of seven of the established GBM cell lines expressed both non-spliced and spliced AIM-2. Furthermore, the C9 CTL clone, which is specific for AIM-2 peptide (RSDSGQQARY), efficiently recognized GBM tumor cells in an antigen-specific and HLA-A1 restricted manner. IFN-gamma treatment of the GBM tumor cells dramatically increased HLA-A1 expression levels and, consequently, increased CTL recognition of the treated tumor cells. More importantly, seven out of 12 HLA-A1 and AIM-2 positive patients from our dendritic cell clinical trial generated AIM-2 specific CTL activity in their PBMC after vaccinations. These data indicate that AIM-2 could be used as a tumor antigen target for monitoring vaccine trials or to develop antigen specific active immunotherapy for glioma patients.
Insights
Antigen isolated from Immunoselected Melanoma-2 (AIM-2) is expressed in glioblastoma multiforme (GBM). AIM-2 specific T cells recognize and target GBM cells, indicating potential for immunotherapy in glioma patients.
Area of Science:
- * Oncology
- * Immunology
- * Cancer Research
Background:
- * Antigen isolated from Immunoselected Melanoma-2 (AIM-2) is a tumor antigen identified in melanoma.
- * AIM-2 is expressed across various tumor types, including neuroectodermal tumors and carcinomas.
- * Glioblastoma multiforme (GBM) is an aggressive primary brain tumor with limited treatment options.
Purpose of the Study:
- * To investigate the expression of AIM-2 in glioblastoma multiforme (GBM).
- * To evaluate the potential of AIM-2 as a target for immunotherapy in GBM.
- * To assess the clinical relevance of AIM-2 in patients undergoing dendritic cell vaccination.
Main Methods:
- * Analysis of AIM-2 expression in primary GBM cell cultures and established GBM cell lines.
- * Assessment of cytotoxic T lymphocyte (CTL) recognition of GBM cells using AIM-2 specific CTL clones.
- * Evaluation of IFN-gamma treatment effects on HLA-A1 expression and CTL recognition.
- * Monitoring of AIM-2 specific CTL activity in peripheral blood mononuclear cells (PBMC) from patients in a dendritic cell clinical trial.
Main Results:
- * High expression of both non-spliced and spliced AIM-2 was observed in primary GBM cell lines.
- * A majority of established GBM cell lines also expressed both forms of AIM-2.
- * AIM-2 specific CTL clones efficiently recognized GBM tumor cells in an HLA-A1 restricted manner.
- * IFN-gamma treatment enhanced HLA-A1 expression and subsequent CTL recognition of GBM cells.
- * A significant proportion of patients (7/12) with HLA-A1 and AIM-2 positive tumors generated AIM-2 specific CTL activity post-vaccination.
Conclusions:
- * AIM-2 is a relevant tumor antigen expressed in glioblastoma multiforme.
- * AIM-2 specific T cell responses can be generated in GBM patients.
- * AIM-2 represents a promising target for monitoring vaccine trials and developing active immunotherapy for glioma.
