The B7x pathway in the tumor microenvironment

肿瘤微环境中的B7x途径 癌症免疫治疗中的关键问题之一是确定主导的 肿瘤生长不同阶段的逃逸机制及设计方法 去克服它们。我们已经确定B7x是一个特征不佳的成员 B7家族的T细胞共刺激和共抑制。我们的临床数据显示 研究发现，B7x在多种人类中都有异常表达 癌症，往往与不良的临床结果有关。的假说 该项目认为B7x是肿瘤内一条关键的免疫逃避途径 微环境和阻断这一途径产生治疗性肿瘤 豁免权。根据我们发表的癌症患者临床研究和我们的 强大的初步数据与小鼠肿瘤模型，这一假说将得到验证 通过追求三个具体目标：1)阐明 肿瘤表达的B7x在疾病进展中的作用；2)机制的确定 宿主细胞表达的B7x在肿瘤进展中的作用；3)生成 通过靶向B7x途径获得治疗性肿瘤免疫。我们已经产生了 许多新颖的工具，并已组建了一个多学科团队， 技能互补，这为我们提供了解决以下问题的独特机会 挑战和实现目标。这项研究的结果将提供新的 肿瘤中B7x途径免疫逃逸机制的研究进展 为今后的临床设计提供了新的依据 免疫疗法。

The B7x pathway in the tumor microenvironment One of the key issues in cancer immunotherapy is to identify the dominant escape mechanisms during different phases of tumor growth and to devise ways to overcome them. We have identified B7x as a poorly characterized member of the B7 family of T cell costimulation and coinhibition. Our clinical data have revealed that aberrant expression of B7x is observed in a variety of human cancers and is often associated with poor clinical outcome. The hypothesis of this project is that B7x is a critical immune evasion pathway within the tumor microenvironment and blockade of this pathway generates therapeutic tumor immunity. Guided by our published clinical research with cancer patients and our strong preliminary data with murine tumor models, this hypothesis will be tested by pursuing three specific aims: 1) Elucidation of the functional consequence of tumor-expressed B7x in disease progression; 2) Determination of mechanistic contribution of host cell-expressed B7x to tumor progression; and 3) Generation of therapeutic tumor immunity by targeting the B7x pathway. We have generated a number of novel tools and have assembled a multi-disciplinary team with complementary skill sets, which provides us with unique opportunities to address challenges and realize goals. The outcomes of this research will provide novel insights into immune evasion mechanisms of the B7x pathway in the tumor microenvironment and provide the basis for future clinical design of a new immunotherapy.