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Updated: May 15, 2026
Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
Characterization of Ewing sarcoma associated cancer/testis antigens
Dorothea E Mahlendorf1, Martin Sebastian Staege
1Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Abstract:
The prognosis of patients suffering from tumors of the Ewing family (EFT) is still poor. Immunotherapy strategies are pursued and EFT-specific antigens have to be identified as targets for cytotoxic T-lymphocytes (CTL). Due to the lack of expression of cancer/testis antigens (CTA) in normal tissues, these antigens are partially able to induce immune responses in cancer patients. Therefore, they are promising targets for immunotherapy. EFT are characterized by chromosomal rearrangements involving members of the TET (translocated in liposarcoma, Ewing sarcoma breakpoint region 1, TATA box binding protein-associated factor 15) family of RNA binding proteins and members of the E-26 (ETS) family of transcription factors. The resulting onco-fusion proteins are highly specific for EFT and downstream targets of TET-ETS represent candidate tumor specific antigens. In order to identify new EFT-associated CTA, we analyzed microarray-data sets from EFT and normal tissues from the Gene Expression Omnibus (GEO) database. The impact of TET-ETS on expression of CTA was analyzed using GEO data sets from transgenic mesenchymal stem cells. One CTA with high specificity for EFT is lipase I (LIPI, membrane-associated phospholipase A1-β). CTL specific for LIPI-derived peptides LDYTDAKFV and NLLKHGASL were able to lyse HLA-A2 positive EFT cells in vitro which confirms the possible role of LIPI and other CTA for EFT-immunotherapy.
Insights
Identifying new targets for immunotherapy is crucial for treating Ewing family of tumors (EFT). Lipase I (LIPI) is a promising cancer/testis antigen (CTA) found to be specifically expressed in EFT, showing potential for T-cell based therapies.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Ewing family of tumors (EFT) have a poor prognosis, necessitating novel therapeutic strategies.
- Immunotherapy, particularly targeting cancer/testis antigens (CTA), offers a promising avenue for EFT treatment.
- EFT are defined by specific chromosomal rearrangements involving TET and ETS family proteins, creating unique onco-fusion proteins.
Purpose of the Study:
- To identify novel EFT-specific CTA for immunotherapy.
- To investigate the role of TET-ETS oncoprotein in CTA expression.
- To evaluate the potential of identified CTA as targets for cytotoxic T-lymphocyte (CTL) therapy.
Main Methods:
- Analysis of microarray datasets from the Gene Expression Omnibus (GEO) database for EFT and normal tissues.
- Examination of GEO datasets from transgenic mesenchymal stem cells to assess the impact of TET-ETS on CTA expression.
- In vitro assays using CTLs specific for identified CTA peptides against HLA-A2 positive EFT cells.
Main Results:
- Lipase I (LIPI), a membrane-associated phospholipase A1-β, was identified as a CTA with high specificity for EFT.
- TET-ETS fusion proteins influence the expression of specific CTA in EFT.
- CTLs targeting LIPI-derived peptides (LDYTDAKFV and NLLKHGASL) demonstrated efficacy in lysing HLA-A2 positive EFT cells in vitro.
Conclusions:
- LIPI is a potential tumor-specific antigen for EFT immunotherapy.
- Targeting LIPI with CTLs represents a viable strategy for EFT treatment.
- Further investigation into LIPI and other CTA could advance EFT immunotherapy.
