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Published on: January 9, 2019
Identification of SOX2 as a novel glioma-associated antigen and potential target for T cell-based immunotherapy
1Medical Faculty, Institute of Immunology, Technical University of Dresden, Dresden, Germany.
Abstract:
Prognosis for patients suffering from malignant glioma has not substantially improved. Specific immunotherapy as a novel treatment concept critically depends on target antigens, which are highly overexpressed in the majority of gliomas, but the number of such antigens is still very limited. SOX2 was identified by screening an expression database for transcripts that are overexpressed in malignant glioma, but display minimal expression in normal tissues. Expression of SOX2 mRNA was further investigated in tumour and normal tissues by real-time PCR. Compared to cDNA from pooled normal brain, SOX2 was overexpressed in almost all (9 out of 10) malignant glioma samples, whereas expression in other, non-malignant tissues was almost negligible. SOX2 protein expression in glioma cell lines and tumour tissues was verified by Western blot and immunofluorescence. Immunohistochemistry demonstrated SOX2 protein expression in all malignant glioma tissues investigated ranging from 6 to 66% stained tumour cells. Human leucocyte antigen-A(*)0201-restricted SOX2-derived peptides were tested for the activation of glioma-reactive CD8+ cytotoxic T lymphocytes (CTLs). Specific CTLs were raised against the peptide TLMKKDKYTL and were capable of lysing glioma cells. The abundant and glioma-restricted overexpression of SOX2 and the generation of SOX2-specific and tumour-reactive CTLs may recommend this antigen as target for T-cell-based immunotherapy of glioma.
Insights
SOX2 is overexpressed in malignant glioma, making it a potential target for immunotherapy. Researchers generated SOX2-specific cytotoxic T lymphocytes (CTLs) capable of targeting and lysing glioma cells, offering a new avenue for cancer treatment.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Malignant glioma prognosis remains poor, necessitating novel therapeutic strategies.
- Effective immunotherapy requires identifying highly glioma-specific target antigens.
- Current options for glioma-specific antigens are limited.
Purpose of the Study:
- To identify novel glioma-specific antigens for immunotherapy.
- To investigate the potential of SOX2 as a target antigen for glioma immunotherapy.
Main Methods:
- SOX2 expression analysis in glioma and normal tissues using real-time PCR.
- SOX2 protein validation via Western blot and immunofluorescence.
- Generation and testing of SOX2-specific cytotoxic T lymphocytes (CTLs) against glioma cells.
Main Results:
- SOX2 mRNA and protein were significantly overexpressed in malignant glioma tissues compared to normal tissues.
- SOX2 expression ranged from 6% to 66% in malignant glioma tissues.
- SOX2-specific CTLs demonstrated the ability to lyse glioma cells.
Conclusions:
- SOX2 is a glioma-restricted antigen with abundant overexpression, suitable for immunotherapy.
- SOX2-derived peptides can activate tumor-reactive CTLs.
- SOX2 represents a promising target for T-cell-based glioma immunotherapy.
