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Shared Placenta/Tumor Antigens and Maternal Immunity

共享胎盘/肿瘤抗原和母体免疫

基本信息

批准号：
9316903
负责人：
MARGARET G PETROFF
金额：
$ 23.25万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-18 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9316903
关键词：
Adult Antigens Blood Breast Cancer Cell CTAG1 gene Cancer Etiology Cancer Vaccines Cancerous Cells Clinical Data Decidua Development Disease Progression Esophageal Squamous Cell Carcinoma Etiology Fetus Flow Cytometry Future Glycoproteins HLA Antigens Histocompatibility Antigens Hormonal Human Immune Immune response Immune system Immunity Immunologics Inherited Lead Light Lymphocyte Major Histocompatibility Complex Malignant Neoplasms Mammary Neoplasms Mediating Medical Modeling Mothers Mus New York Normal tissue morphology Nulliparity Ovalbumin Pattern Physiological Placenta Positioning Attribute Predisposition Pregnancy Property Proteins Research Personnel Resistance Risk Risk Reduction T cell response T-Lymphocyte Testing Therapeutic Time Tissues Transgenic Organisms Tumor Antigens Tumor Immunity Woman Work acronyms cancer prevention cancer risk clinically relevant cohort embryo/fetus antigen experimental study fetal immunogenic in vivo insight interest lifetime risk malignant breast neoplasm mouse model neoplastic cell novel parity peripheral blood placenta neoplasm pregnant stem cell differentiation theories trophoblast tumor

项目摘要

Project Summary/Abstract Pregnancy impacts the maternal immune system and breast cancer risk, but whether these effects are related is unknown. Many women are immunologically primed to fetal antigens during pregnancy due to the unique expression of paternally- inherited antigens by the fetus. However, whether this priming has any consequence on subsequent progression of diseases in women is unknown. Tumor antigens are proteins that have limited expression in normal adult tissues, but are strongly expressed in many cancers, including cancer of the breast. Because of their ability to induce immunity, there is strong scientific and medical interest in exploiting this property for development of anti-cancer vaccines. Despite their restricted expression patterns, several, which we call shared placenta/tumor antigens, are highly expressed in the placenta. Investigators have long speculated that trophoblast cells and tumor cells share similarities, but the immunologic relationship between shared placenta/tumor antigens, breast cancer, and pregnancy are completely unknown. In this proposal, we explore the hypothesis that shared tumor/placenta antigens are immunogenic during pregnancy. These experiments serve as critical proof of concept experiments, with which we can further explore the long term hypothesis that immune priming to shared placenta tumor antigens during pregnancy alter breast cancer risk in parous women. To determine whether the placenta primes the maternal immune system against shared placenta/tumor antigens, we propose the following Specific Aims: 1. Determine whether the murine maternal immune system is primed to shared tumor/placenta antigens. 2. Test women for evidence of sensitization to shared placenta/tumor antigens. To our knowledge, this is the first time that a long-term consequence of the physiologically normal maternal immune response to fetal antigens will be considered in light of a critical clinical problem: women's cancer. In the long-term, this work could profoundly impact our understanding of why parity changes risk of breast cancer, and lead to insights into novel cancer prevention and therapeutic strategies.

项目总结/文摘