Role of inflammation in cancer progression

炎症在癌症进展中的作用

基本信息

批准号：
8750502
负责人：
Yiping Yang
金额：
$ 20.51万
依托单位：
DUKE UNIVERSITY
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：
2014-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8750502
关键词：
Address Age Antigens CCL2 gene CCRL2 gene Cells Chronic Development Distant Metastasis Dysplasia Granulocyte-Macrophage Colony-Stimulating Factor Growth Hematopoietic Hematopoietic stem cells Hepatic Hepatitis Hepatocyte ITGAM gene Immune Immune response Immunosuppressive Agents In Vitro Inflammation Inflammatory Lead Lesion Life Liver Malignant - descriptor Malignant Neoplasms Mediating Modeling Multipotent Stem Cells Mus Nodule Organ Phase Play Premalignant Primary carcinoma of the liver cells Production Proto-Oncogene Protein c-kit RANTES Recruitment Activity Relapse Role Signal Pathway Signal Transduction Staging T cell response Testing Therapeutic Time Tumor-Derived War Work adenoma cancer prevention cancer therapy chemokine receptor design immune clearance innovation monocyte new therapeutic target prevent public health relevance response tumor tumor progression tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Recent advances have highlighted an important role for chronic inflammation in promoting tumor development. How chronic inflammation promotes tumor formation during the early stages of tumorigenesis remains unknown. In the preliminary studies, we investigated whether MyD88, a common adaptor for the innate immune signaling pathways, plays a role in the development of inflammation-induced, spontaneously developed hepatocellular carcinoma (HCC). We showed that hepatocyte-intrinsic MyD88 signaling is critical for the development of the precancerous dysplastic nodules and their progression to HCC. The objective of this application is to elucidate critical mechanisms governing the immune evasion by precancerous dysplastic lesions, leading to progression to HCC. Specifically, we hypothesize that precancerous dysplastic hepatocytes evade immune elimination by recruiting immunosuppressive inflammatory monocytes. We will test this hypothesis and pursue the critical tumor-derived factors involved in the recruitment of the immune suppressors. By providing how tumor-derived factors influence the anti-tumor immune response during the early time points of tumorigenesis, these studies will have profound implications in the development of new therapeutic targets for cancer prevention and therapy.

描述（由申请人提供）：最近的进步强调了慢性炎症在促进肿瘤发育中的重要作用。在肿瘤发生的早期阶段，慢性炎症如何促进肿瘤形成仍然未知。在初步研究中，我们调查了MyD88是先天免疫信号通路的常见适配器，在炎症引起的，自发发展的肝细胞癌（HCC）中起作用。我们表明，肝细胞内MyD88信号对于癌前发育不良结节的发展至关重要，它们的发展为HCC至关重要。该应用的目的是阐明癌前发育不良病变管理免疫逃避的关键机制，从而导致hcc的发展。具体而言，我们假设癌前发育不良的肝细胞通过募集免疫抑制性炎症单核细胞来逃避免疫消除。我们将检验这一假设，并追求参与免疫抑制子募集的关键肿瘤衍生因素。通过提供肿瘤衍生的因素如何影响肿瘤发生早期点期间的抗肿瘤免疫反应，这些研究将对预防癌症预防和治疗的新治疗靶点的发展具有深远的影响。