Shared Placenta/Tumor Antigens and Maternal Immunity

项目摘要/摘要 怀孕会影响母亲的免疫系统和乳腺癌风险，但这些影响是否相关尚不清楚。 许多女性在怀孕期间对胎儿抗原具有免疫预备性，这是因为父系特有的- 胎儿遗传的抗原。然而，这种启动是否会对随后的进展产生任何影响 女性中的疾病是未知的。 肿瘤抗原是一种蛋白质，在正常成人组织中表达有限，但在许多组织中强烈表达。 癌症，包括乳腺癌。由于它们具有诱导免疫的能力，所以有很强的科学和医学基础 有兴趣利用这一特性开发抗癌疫苗。尽管它们的表达模式受到限制， 几种我们称之为共享胎盘/肿瘤抗原的抗原在胎盘中高度表达。调查人员长期以来 推测滋养层细胞和肿瘤细胞有相似之处，但两者之间的免疫学关系相同 胎盘/肿瘤抗原、乳腺癌和怀孕是完全未知的。在本提案中，我们探讨了 假设共同的肿瘤/胎盘抗原在怀孕期间具有免疫原性。这些实验是至关重要的 概念验证实验，通过这些实验，我们可以进一步探索免疫启动共享的长期假说 孕期胎盘肿瘤抗原改变临产妇女患乳腺癌的风险。以确定胎盘是否 为了启动母体免疫系统对抗共同的胎盘/肿瘤抗原，我们提出了以下具体目标： 1.确定小鼠母体免疫系统是否为共享的肿瘤/胎盘抗原做好了准备。 2.测试女性对共同的胎盘/肿瘤抗原敏感的证据。 据我们所知，这是第一次出现生理上正常的母体免疫的长期后果 对胎儿抗原的反应将根据一个关键的临床问题来考虑：妇女的癌症。从长远来看，这 这项工作可能会深刻地影响我们对为什么产次改变乳腺癌风险的理解，并导致对 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.