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Role of extracellular matrix remodeling on high-grade serous ovarian carcinoma immune evasion

细胞外基质重塑在高级别浆液性卵巢癌免疫逃避中的作用

基本信息

批准号：
10425569
负责人：
Pilar de la Puente
金额：
$ 23.28万
依托单位：
SANFORD RESEARCH/USD
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10425569
关键词：
3-Dimensional Action Research Address Affect Animals Antitumor Response Attenuated Biochemical Biological Biological Assay Cell Communication Cells Data Development Drug resistance Engineering Exclusion Experimental Models Extracellular Matrix Goals Hypoxia Immune Immune Evasion Immune response Immunologic Surveillance Immunosuppression Immunotherapy Impairment Incidence Infiltration Malignant Epithelial Cell Malignant Neoplasms Malignant neoplasm of ovary Mind Modeling Nature Ovarian Serous Adenocarcinoma Oxygen Patients Positioning Attribute Pre-Clinical Model Recreation Research Methodology Research Priority Role Sampling System T-Lymphocyte Testing Time Tissues Tumor Escape Tumor Tissue Tumor-Infiltrating Lymphocytes Tumor-infiltrating immune cells Woman Work base cancer cell cancer subtypes cell behavior cost experimental study immune checkpoint immune checkpoint blockade immune function improved outcome insight mechanical properties meetings new technology novel novel strategies ovarian neoplasm prognostic indicator reconstruction response three-dimensional modeling tissue culture tumor tumor hypoxia tumor microenvironment tumor progression

项目摘要

The broad goal of the proposed work is to understand how the hypoxia-induced extracellular matrix (ECM) remodeling in ovarian cancer affects immune evasion. Understanding this concept would have a broad impact on identifying effective immunotherapies for ovarian cancer, a particularly deadly form of cancer in women. The ECM not only provides structural and biochemical support to tumor tissue, but also the ECM undergoes remodeling which alters the composition and mechanical properties of the tumor microenvironment, directly influencing immune evasion mechanisms. With this in mind, it has been established that hypoxia can influence tumor immunosuppression and this inadequate tissue oxygen, or hypoxia, promotes ECM remodeling. However, little is known about the role of the hypoxia-induced ECM in immune evasion and response to immunotherapy in ovarian cancer. Unfortunately, there is a scarcity of preclinical models providing recapitulation of the hypoxia-induced ECM remodeling of ovarian tumors. Thus, new technologies that allow the study of the hypoxia-induced ECM remodeling and its impact on immune evasion are crucially required. In studies leading to this application, we developed a patient-derived 3D tissue culture system capable of recapitulating the hypoxia-induced ECM and tumor-immune interactions. Specifically, we will utilize engineering approaches and patient-derived samples in order to assess the effect of the hypoxia-induced ECM remodeling on the tumor-immune cycle and further validate new treatments to overcome immune evasion. Successful completion of the proposed work will allow us to investigate the role of the hypoxia-induced ECM remodeling on cancer immune evasion, to identify how tumors escape immune surveillance, and to ascertain novel strategies to re-sensitize cancer cells to immune cells reducing tumor immune evasion in a precision-based manner.

所提出的工作的总体目标是了解缺氧诱导的细胞外基质（ECM）