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The impact of exposure to allergic inflammation on esophageal carcinogenesis

接触过敏性炎症对食管癌发生的影响

基本信息

批准号：
10308094
负责人：
Kelly A Whelan
金额：
$ 18.15万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-01 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10308094
关键词：
Allergic Allergic inflammation Antitumor Response Apoptosis Apoptotic Basal Cell Bioinformatics CD8-Positive T-Lymphocytes Cancer Etiology Cancer Patient Cell Compartmentation Cell Death Cells Chronic Clinical Coculture Techniques Data Development Diagnosis Eosinophilia Eosinophilic Esophagitis Epithelial Epithelial Cells Esophageal Adenocarcinoma Esophageal Neoplasms Esophagitis Esophagus Event Exposure to Future Gastroesophageal reflux disease Goals Hypersensitivity IgE Immune Immune response Inflammation Inflammatory Investigation Knowledge Malignant Neoplasms Malignant neoplasm of esophagus Mediating Mediator of activation protein Modeling Molecular Monitor Mononuclear Mus Organ Outcome Patient-Focused Outcomes Patients Peptic Esophagitis Plant Roots Population Population Study Prevention therapy Reflux Risk Factors Signal Transduction System Testing Tumor Cell Line antitumor effect base cancer prevention cancer risk carcinogenesis clinical care eosinophil epidemiologic data epidemiology study esophageal cancer prevention esophageal carcinogenesis food allergen genetic signature improved in vivo mortality mouse model neoplastic cell novel novel strategies peripheral blood pre-clinical progenitor single-cell RNA sequencing translational impact

项目摘要

Project Summary Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer mortality worldwide. Chronic reflux-associated esophagitis, termed gastroesophageal reflux disease (GERD), is a primary risk factor for development of esophageal adenocarcinoma. Eosinophilic esophagitis (EoE) represents food allergen-mediated esophagitis characterized by esophageal eosinophilia. In contrast to patients with reflux esophagitis, epidemiological data indicates that EoE patients fail to develop esophageal cancer despite the presence of chronic esophageal inflammation. A negative correlation between allergic inflammation and cancer risk has been identified in a variety of organs via population-based studies; however, functional investigations are necessary to define the relationship between allergy and cancer as well as to determine the feasibility of approaches for leveraging allergic inflammation to improve clinical outcomes in cancer patients. To examine the relationship between EoE and cancer, we paired murine models of the two conditions. Our robust preliminary data indicate that exposure to EoE inflammation limits esophageal carcinogenesis in vivo. We hypothesize that EoE inflammation limits esophageal carcinogenesis by activating anti-tumor responses in the immune and epithelial cell compartments. We will test this hypothesis by pursuing the following Specific Aims: Aim 1: Identify the immune-mediated mechanisms responsible for tumor cell apoptosis induced by EoE inflammation. Aim 2: Delineate the impact of EoE inflammation upon esophageal epithelial cells in the context of carcinogenesis. These studies provide the first functional investigation of the relationship between EoE and esophageal cancer with the potential to unveil novel mechanisms for targeting the allergic immune response and/or allergy-mediated esophageal epithelial fate decisions to improve clinical care for cancer patients. These developmental R21 studies will identify the direct cellular/molecular mechanisms through which the EoE influences the epithelial and immune cell compartments to limit esophageal carcinogenesis. A future R01 proposal will aggressively pursue identified mechanisms in preclinical and clinical models to meet our long- term goal of defining novel strategies for improving esophageal cancer prevention, diagnosis, monitoring, and therapy. As a negative association between allergic inflammation and cancer has been identified in various organs, findings from this study may have broad implications for cancer prevention and therapy.

项目总结