Shared Placenta/Tumor Antigens and Maternal Immunity

项目概要/摘要 怀孕会影响母体免疫系统和乳腺癌风险，但这些影响是否相关尚不清楚。 许多妇女在怀孕期间对胎儿抗原进行免疫致敏，这是由于父系- 胎儿遗传的抗原。然而，这种启动是否对随后的进展有任何影响， 女性的疾病是未知的。 肿瘤抗原是在正常成人组织中具有有限表达，但在许多成人组织中强烈表达的蛋白质。 癌症，包括乳腺癌。由于其诱导免疫的能力，有很强的科学性和医学性， 开发这种特性用于开发抗癌疫苗的兴趣。尽管它们的表达模式有限， 我们称之为共享胎盘/肿瘤抗原的几种抗原在胎盘中高度表达。调查人员一直 推测滋养层细胞和肿瘤细胞有相似之处，但它们之间的免疫关系 胎盘/肿瘤抗原、乳腺癌和妊娠完全未知。在本建议中，我们探讨 共同的肿瘤/胎盘抗原在妊娠期间具有免疫原性的假设。这些实验对于 概念验证实验，我们可以进一步探讨免疫启动共享的长期假设， 妊娠期间胎盘肿瘤抗原改变经产妇女患乳腺癌的风险以确定胎盘是否 启动母体免疫系统对抗共有的胎盘/肿瘤抗原，我们提出以下具体目标： 1.确定小鼠母体免疫系统是否对共有的肿瘤/胎盘抗原进行了致敏。 2.测试妇女是否对共有胎盘/肿瘤抗原过敏。 据我们所知，这是第一次，一个长期的后果，生理正常的孕产妇免疫 对胎儿抗原的反应将根据一个关键的临床问题：妇女癌症来考虑。从长远来看，这 这项工作可能会深刻地影响我们对为什么生育会改变乳腺癌风险的理解，并导致对以下问题的深入了解： 新的癌症预防和治疗策略。

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.