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Published on: October 30, 2013
The human T-box mesodermal transcription factor Brachyury is a candidate target for T-cell-mediated cancer
Claudia Palena1, Dmitry E Polev, Kwong Y Tsang
1Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Purpose:
Identification of tumor antigens is essential in advancing immune-based therapeutic interventions in cancer. Particularly attractive targets are those molecules that are selectively expressed by malignant cells and that are also essential for tumor progression.
Experimental Design And Results:
We have used a computer-based differential display analysis tool for mining of expressed sequence tag clusters in the human Unigene database and identified Brachyury as a novel tumor antigen. Brachyury, a member of the T-box transcription factor family, is a key player in mesoderm specification during embryonic development. Moreover, transcription factors that control mesoderm have been implicated in the epithelial-mesenchymal transition (EMT), which has been postulated to be a key step during tumor progression to metastasis. Reverse transcription-PCR analysis validated the in silico predictions and showed Brachyury expression in tumors of the small intestine, stomach, kidney, bladder, uterus, ovary, and testis, as well as in cell lines derived from lung, colon, and prostate carcinomas, but not in the vast majority of the normal tissues tested. An HLA-A0201 epitope of human Brachyury was identified that was able to expand T lymphocytes from blood of cancer patients and normal donors with the ability to lyse Brachyury-expressing tumor cells.
Conclusions:
To our knowledge, this is the first demonstration that (a) a T-box transcription factor and (b) a molecule implicated in mesodermal development, i.e., EMT, can be a potential target for human T-cell-mediated cancer immunotherapy.
Insights
Researchers identified Brachyury, a transcription factor involved in embryonic development, as a novel tumor antigen. This finding opens new avenues for T-cell-mediated cancer immunotherapy targeting Brachyury-expressing tumors.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Tumor antigen identification is crucial for developing effective cancer immunotherapies.
- Ideal tumor antigens are selectively expressed in cancer cells and vital for tumor growth and metastasis.
Purpose of the Study:
- To identify novel tumor antigens for cancer immunotherapy.
- To investigate Brachyury as a potential target for T-cell-mediated cancer treatment.
Main Methods:
- Bioinformatic analysis of expressed sequence tag clusters in the human Unigene database.
- Reverse transcription-polymerase chain reaction (RT-PCR) to validate gene expression.
- Identification of HLA-A0201 epitope for T-cell expansion and tumor cell lysis.
Main Results:
- Brachyury was identified as a novel tumor antigen using computational analysis.
- Brachyury expression was confirmed in various tumor types (small intestine, stomach, kidney, bladder, uterus, ovary, testis, lung, colon, prostate) but not in most normal tissues.
- An HLA-A0201 epitope of Brachyury successfully expanded T lymphocytes capable of lysing tumor cells.
Conclusions:
- Brachyury, a T-box transcription factor involved in mesodermal development and epithelial-mesenchymal transition (EMT), is a promising target for cancer immunotherapy.
- This study represents the first demonstration of a T-box transcription factor implicated in EMT as a target for human T-cell-mediated cancer immunotherapy.
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