p53-Mediated Tumor Immune Surveillance

p53 介导的肿瘤免疫监视

基本信息

批准号：
8985286
负责人：
David Feldser
金额：
$ 36.6万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8985286
关键词：
Activated Natural Killer Cell Acute Biological CD80 gene Cell Culture System Cell Line Cell Surface Proteins Cell Survival Cell surface Cells Cessation of life Clinical Cytoplasmic Granules Data Data Set Development Disabled Persons Disease Environment Exocytosis Future Gene Deletion Gene Expression Genes Genetically Engineered Mouse Goals Human Immune system Immunologic Surveillance Interferons Knowledge Lead Lesion Ligands Lung Adenocarcinoma Lymphocyte Malignant Neoplasms Malignant neoplasm of lung Measures Mediating Medicine Modeling Molecular Molecular Profiling Mus Mutate Mutation NK Cell Activation Natural Killer Cells Oncogenes Oncogenic Outcome Pathway interactions Patients Physiological Population Positioning Attribute Process Protein p53 Proteins Publishing Research Role Signal Transduction Surface System Testing Time Tissue Microarray Tissues Translating Tumor Suppression Tumor Suppressor Genes Tumor Suppressor Proteins Tumor-Derived Work base cancer cell cancer therapy cancer type gene function in vivo innovation insight killings knock-down mouse model mutant neoplastic cell neutralizing antibody novel outcome forecast prognostic value programs public health relevance receptor response restoration therapy development treatment strategy tumor tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Our research is focused on understanding the multistep process of tumorigenesis and the mechanisms that suppress tumor formation and progression. We have developed systems from genetically engineered mice to uncover and deconstruct the timing and mechanism of action for tumor suppressor genes commonly mutated in human cancers. Our work here focuses on a lung adenocarcinoma, a common malignancy associated with poor prognosis. Additionally, we focus on the p53 tumor suppressor as it is the most frequently mutated gene in this cancer type. We employ a strategy that allows the temporal control over p53 actions in established murine lung adenocarcinomas that allows us to determine the relevant biological programs that ensue upon p53 action in these cancers. We have identified a non-cancer cell autonomous program of tumor regression that requires natural killer cells. Our innovative strategy and unique in vivo and cell culture systems afford us the ability to interrogate the roles of specific molecules regulated by p53 in the cancer and the physiological response of natural killer cells as they mediate tumor regression. Our goal here is to mechanistically define this tumor suppressive pathway. These insights will be important for future work aimed at developing tumoricidal natural killer cells that could be used as a cell-based anti- cancer therapy.

描述（由申请人提供）：我们的研究重点是了解肿瘤发生的多步骤过程以及抑制肿瘤形成和进展的机制。我们开发了来自基因工程小鼠的系统，以揭示和解构肿瘤抑制基因的作用时间和机制。我们在这里的工作重点是肺腺癌，这是一种与预后不良相关的常见恶性肿瘤。此外，我们还关注 p53 肿瘤抑制基因，因为它是最常见的突变基因。在这种癌症类型中，我们采用了一种策略，可以对已建立的小鼠肺腺癌中的 p53 作用进行时间控制，从而使我们能够确定这些癌症中 p53 作用后发生的相关生物程序。我们的创新策略和独特的体内和细胞培养系统使我们能够探究 p53 调节的特定分子在癌症中的作用以及自然杀伤细胞介导的生理反应。肿瘤消退。我们的目标是机械地定义这种肿瘤抑制途径，这些见解对于未来旨在开发可用作基于细胞的抗癌疗法的杀肿瘤自然杀伤细胞的工作非常重要。