title: Immune Targeting of Tumor Epithelial-Mesenchymal Transition via Brachyury-Based Vaccines.
abstract: As a manifestation of their inherent plasticity, carcinoma cells undergo profound phenotypic changes during progression toward metastasis. One such phenotypic modulation is the epithelial-mesenchymal transition (EMT), an embryonically relevant process that can be reinstated by tumor cells, resulting in the acquisition of metastatic propensity, stem-like cell properties, and resistance to a variety of anticancer therapies, including chemotherapy, radiation, and some small-molecule targeted therapies. Targeting of the EMT is emerging as a novel intervention against tumor progression. This review focuses on the potential use of cancer vaccine strategies targeting tumor cells that exhibit mesenchymal-like features, with an emphasis on the current status of development of vaccine platforms directed against the T-box transcription factor brachyury, a novel cancer target involved in tumor EMT, stemness, and resistance to therapies. Also presented is a summary of potential mechanisms of resistance to immune-mediated attack driven by EMT and the development of novel combinatorial strategies based on the use of agents that alleviate tumor EMT for an optimized targeting of plastic tumor cells that are responsible for tumor recurrence and the establishment of therapeutic refractoriness.
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: palenac@mail.nih.gov.
authors.forename: Claudia
authors.initials: C
authors.lastname: Palena
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: hamiltondh@mail.nih.gov.
authors.forename: Duane H
authors.initials: DH
authors.lastname: Hamilton
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D058750:Epithelial-Mesenchymal Transition / Q000276:immunology*; D005326:Fetal Proteins / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D020825:T-Box Domain Proteins / Q000276:immunology*; D000098908:Brachyury Protein
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein
keywords: Brachyury; Cancer vaccines; EMT; Stemness; Therapeutic resistance; Tumor progression