Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Semin Oncol. 2012 Jun;39(3):358-66. doi: 10.1053/j.seminoncol.2012.02.005.
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.
上皮-间充质转化（EMT）被认为是癌细胞转移过程中的一个关键步骤。经历 EMT 的肿瘤细胞不仅获得了运动性和侵袭性，还对许多传统的癌症治疗方式，包括化疗和放疗，产生了更高的耐药性。因此，EMT 已成为针对肿瘤转移的治疗干预的一个有吸引力的、潜在的靶向过程。EMT 过程由一组被指定为 EMT 转录因子的转录因子驱动，例如 Snail、Slug、Twist 和最近发现的 T 盒家族成员 Brachyury。为了确定 EMT 的这些驱动因素中哪一个更适合靶向治疗，特别是 T 细胞介导的免疫治疗方法，我们检查了它们在一系列人类和鼠类正常组织、癌细胞系和人类肿瘤活检中的相对表达水平。我们的结果表明，Brachyury 是一种在人类肿瘤中表达模式高度受限的分子。我们还证明了 Brachyury 具有免疫原性，并且在体外扩增的 Brachyury 特异性 CD8(+) T 细胞能够裂解 Brachyury 阳性肿瘤细胞。因此，我们提出 Brachyury 作为一种有吸引力的靶标，用于设计专门针对经历 EMT 的肿瘤细胞的疫苗策略。
