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The B7x pathway in the tumor microenvironment

肿瘤微环境中的 B7x 通路

基本信息

批准号：
8631219
负责人：
Xingxing Zang
金额：
$ 34.65万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8631219
关键词：
Address B7-DC antigen CD28 gene CD80 gene Cancer Patient Cell Line Cell physiology Cells Clinical Clinical Data Clinical Research Clinical Trials Data Development Disease Progression Effectiveness Evolution Family Future Generations Genes Goals Histamine H3 Receptors Human Immune Immune response Immunity Immunosuppressive Agents Immunotherapeutic agent Immunotherapy Investigation Islet Cell Kinetics Knock-out Knockout Mice Knowledge Lead Lymphoid Tissue Malignant Neoplasms Malignant neoplasm of ovary Malignant neoplasm of prostate Mammary Neoplasms Mission Modeling Monoclonal Antibodies Mus Myelogenous Neoplasm Metastasis Outcome Outcomes Research Pancreas Pathway interactions Patients Phase Positioning Attribute Proteins Public Health Publishing Reagent Regulatory T-Lymphocyte Research Resistance Role Staging Structure Suppressor-Effector T-Lymphocytes System T-Cell Activation T-Lymphocyte Testing Therapeutic Tissues Transgenic Mice Translating Tumor Burden Tumor Immunity Work base cancer cell cancer immunotherapy cohort design in vivo innovation insight melanoma member mouse model neoplastic cell novel overexpression programs public health relevance receptor skills therapeutic target tool tumor tumor growth tumor microenvironment tumor progression tumorigenesis

项目摘要

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.

肿瘤微环境中的 B7x 通路癌症免疫治疗的关键问题之一是确定占主导地位的肿瘤生长不同阶段的逃逸机制并设计方法去克服它们。我们已将 B7x 确定为特征较差的成员 T 细胞共刺激和共抑制的 B7 家族。我们的临床数据有揭示在多种人类中观察到 B7x 的异常表达癌症，并且通常与不良的临床结果相关。的假设该项目表明 B7x 是肿瘤内关键的免疫逃避途径微环境和该途径的阻断产生治疗性肿瘤免疫。以我们发表的癌症患者临床研究和我们的研究为指导小鼠肿瘤模型的强有力的初步数据，这一假设将得到检验通过追求三个具体目标：1）阐明功能性后果肿瘤表达的 B7x 在疾病进展中的作用； 2) 机理的测定宿主细胞表达的 B7x 对肿瘤进展的贡献； 3) 一代通过靶向 B7x 途径来治疗肿瘤免疫。我们已经生成了一些新颖的工具，并组建了一个多学科团队互补的技能组合，为我们提供了独特的机会来解决挑战并实现目标。这项研究的成果将提供新颖的深入了解肿瘤中 B7x 通路的免疫逃避机制微环境，为未来新药的临床设计提供基础免疫疗法。