title: Cancer vaccines targeting the epithelial-mesenchymal transition: tissue distribution of brachyury and other drivers of the mesenchymal-like phenotype of carcinomas.
abstract: The epithelial-mesenchymal transition (EMT) is thought to be a critical step along the metastasis of carcinomas. In addition to gaining motility and invasiveness, tumor cells that undergo EMT also acquire increased resistance to many traditional cancer treatment modalities, including chemotherapy and radiation. As such, EMT has become an attractive, potentially targetable process for therapeutic interventions against tumor metastasis. The process of EMT is driven by a group of transcription factors designated as EMT transcription factors, such as Snail, Slug, Twist, and the recently identified T-box family member, Brachyury. In an attempt to determine which of these drivers of EMT is more amenable to targeted therapies and, in particular, T-cell-mediated immunotherapeutic approaches, we have examined their relative expression levels in a range of human and murine normal tissues, cancer cell lines, and human tumor biopsies. Our results demonstrated that Brachyury is a molecule with a highly restricted human tumor expression pattern. We also demonstrated that Brachyury is immunogenic and that Brachyury-specific CD8(+) T cells expanded in vitro are able to lyse Brachyury-positive tumor cells. We thus propose Brachyury as an attractive target for vaccination strategies designed to specifically target tumor cells undergoing EMT.
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Duane H
authors.initials: DH
authors.lastname: Hamilton
authors.forename: Mary T
authors.initials: MT
authors.lastname: Litzinger
authors.forename: Romaine I
authors.initials: RI
authors.lastname: Fernando
authors.forename: Bruce
authors.initials: B
authors.lastname: Huang
authors.forename: Claudia
authors.initials: C
authors.lastname: Palena
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000276:immunology*; D005326:Fetal Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000098908:Brachyury Protein
chemical_list: D019496:Cancer Vaccines; D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein