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Epithelium-derived alarmins role in breast cancer immunoprevention

上皮源性警报素在乳腺癌免疫预防中的作用

基本信息

批准号：
9788324
负责人：
Shadmehr Demehri
金额：
$ 80.19万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9788324
关键词：
Address Allergic inflammation Animal Model Antigen Presentation Automobile Driving BRCA1 gene Biological Assay Blocking Antibodies Breast Breast Cancer Model Breast Cancer Prevention Breast Carcinogenesis Breast Epithelial Cells CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes Cancer Etiology Cancer Immunology Science Cells Cessation of life Clinic Clinical Clinical Trials DNA Damage DNA Sequence Alteration Development Disease Disseminated Malignant Neoplasm Double-Blind Method Epithelial Epithelial Cells Epithelium Foundations Gland Goals Immune Immune response Immune system Immunity Immunologic Factors Immunotherapeutic agent Immunotherapy In Situ In Vitro Individual Inflammation Interleukins Lead Lesion Malignant - descriptor Malignant Neoplasms Mammary gland Mediating Memory Molecular Nature Outcome Pathway interactions Patients Pattern Phase Premalignant Premalignant Cell Randomized Recurrence Regulatory T-Lymphocyte Research Resolution Role Shapes Signal Transduction Skin Skin Cancer Stress Surveys T cell response T-Cell Activation T-Lymphocyte TSLP gene Testing Therapeutic Therapeutic Uses Tissues Transgenic Animals Tumor Immunity Tumor Suppression United States Woman adaptive immune response adaptive immunity adenoma advanced disease breast lesion cancer invasiveness cancer prevention combat cytokine cytotoxic effector T cell epidemiology study high risk high risk population immune activation knockout animal malignant breast neoplasm mutation carrier neoplastic new therapeutic target novel prevent release factor response skin cancer prevention tumor

项目摘要

Project Summary/Abstract: Advances in cancer immunology has led to the successful use of patients' own immune cells to combat metastatic cancers. However, the therapeutic potential of the immune system in eliminating premalignant cells and preventing their progression to invasive cancers is unclear. To determine the benefit of activating the immune system to prevent cancer development and recurrence, we study the immune pathways that lead to effective immune activation against early phases of breast cancer development. Breast cancer is the most common internal cancer and second cause of cancer deaths among women in the United States. Importantly, the individuals at high risk of developing breast cancer due to underlying genetic mutations and those with premalignant lesions can be clinically identified and treated. Therefore, discovering an effective approach to activate the patients' own immune system against early breast precursor lesions may yield a lasting memory that can prevent breast cancer development and recurrence in this high-risk population. Our previous studies have demonstrated that a skin-derived immune factor called thymic stromal lymphopoietin (TSLP) suppresses the early stages of skin and breast cancer development. We have been able to extend these finding to clinics through a randomized double-blind clinical trial in which we find TSLP induction to promote a robust immune activation against skin cancer precursors and their complete clearance. In order to determine the precise mechanism of TSLP-induced immune response against early premalignant cells in the breast, and to extend our findings to other similar immune factors in high-risk patients, we aim to (1) determine the immune cells and signals that target breast premalignant cells in response to TSLP, (2) investigate the role of other immune factors released by breast cells that can induce immune response to block breast cancer development, and (3) determine the factors that are driving the immune response in the breast glands of patients with genetic mutations and utilize them for induction of an optimal immune response against early breast cancer. The outcomes of the proposed research will establish a foundation for the use of the immune system in blocking breast cancer development and provide novel therapeutic targets for breast cancer immunoprevention.

项目总结/文摘: