Defining an Integrated Allostatic Load Index with Immune and Tumor Microenvironment Factors

研究项目2-项目摘要 MUSC TCC项目的目标是开发更精确的前列腺癌起始生物标志物， 进展，并确定如何治疗和管理前列腺癌的少数民族男子的背景下， 他们的生物风险为不良结果和社会，心理和生理（即，非稳态负荷（AL） 压力源这将使用几种新的创新实验方法直接在存档组织上进行 MUSC独有，使用代表约三分之一非洲人的丰富资源样本队列（n=570） 美国（AA）受试者。基于AA男性中前列腺癌的流行病学（已在 的建议），已作出相当大的努力，以促进早期发现，通过筛查， 前列腺特异性抗原（PSA）检测然而，最近，筛查指南已经从性能 从50岁开始的年度筛查到知情决策，因为新数据已经出现， PSA检测的功效由于早期检测在前列腺癌控制中的作用不那么突出， 更重要的是要确定在启动和进展中激活的生物学途径， 并开发更有效的生物标志物进行早期检测。先前的几项研究表明， 肿瘤微环境和免疫系统之间存在复杂的相互作用， AA男性患上更严重的前列腺癌然而，生物过程 与免疫功能相关的免疫系统在社会环境因素中运作并受其影响。因此，识别 生物学机制，而不了解它们与社会决定因素的联系方式 是必要的，但不足以长期努力减少前列腺癌结局的种族差异 通过疾病的早期发现和临床管理。一个新出现的假设对这一应用至关重要 关于癌症健康差异的一点是，社会条件和对社会压力源的心理反应 影响对癌症的发生和发展至关重要的生物学过程。在这个项目中， MUSC的研究人员将通过一项跨学科研究来检验这一假设， 通过评估肿瘤的发生和发展， 免疫系统、肿瘤糖组、社会决定因素和AL之间的微环境相互作用。 这些研究人员将确定前列腺中不同肿瘤和基质N-聚糖的组合是否 AA男性的癌症促进了更促肿瘤的炎症/免疫微环境。他们还将 研究这些生物过程和社会决定因素之间的关系，包括隔离， 感知压力和慢性社会经济压力源。他们假设压力的组合- 诱导社会决定因素，不同的N-聚糖，免疫/炎症平衡受损， AA人群中的侵袭性前列腺癌。

RESEARCH PROJECT 2- PROJECT SUMMARY The goal of this MUSC TCC project is to develop more precise biomarkers of prostate cancer initiation and progression, and determine how to treat and manage prostate cancer among minority men within the context of their biological risk for poor outcomes and social, psychological, and physiological (i.e., allostatic load/AL) stressors. This will be done using several new innovative experimental approaches directly on archived tissues unique to MUSC, using a rich resource cohort of samples (n=570) representing approximately one third African American (AA) subjects. Based on the epidemiology of prostate cancer among AA men (already described in the proposal), considerable efforts have been made to promote early detection through screening with prostate specific antigen (PSA) testing. Recently, however, screening guidelines have shifted from performance of annual screening starting at age 50 to informed decision-making as new data have emerged about the efficacy of PSA testing. As early detection plays a less prominent role in prostate cancer control, it becomes even more important to identify biological pathways that are activated in the initiation and progression of disease and develop more effective biomarkers for early detection. Several prior studies have shown that there is a complex interplay between the tumor microenvironment and the immune system that contributes to the development of more aggressive prostate cancer among AA men. However, biological processes related to immune functioning operate within and are influenced by social contextual factors. Thus, identifying biological mechanisms without understanding the ways in which they are associated with social determinants is necessary, but not sufficient to long-term efforts to reduce racial disparities in prostate cancer outcomes through early detection and clinical management of disease. An emerging hypothesis central to this application about cancer health disparities is that social conditions and psychological responses to social stressors influence biological processes that are important to the initiation and progression of cancer. In this project, MUSC investigators will examine this hypothesis through a transdisciplinary study that defines the molecular mechanisms involved in the initiation and progression of prostate cancer by evaluating the tumor microenvironment interactions between the immune system, the tumor glycome, social determinants and AL. These investigators will determine whether the combination of distinct tumor and stroma N-glycans in prostate cancers of AA men promotes a more pro-tumor inflammatory/immune microenvironment. They will also examine the relationship between these biological processes and social determinants that include isolation, perceived stress, and chronic socioeconomic stressors. They hypothesize that a combination of stress- inducing social determinants, distinct N-glycans, impaired immune/inflammatory balance contributes to more aggressive prostate cancers in the AA population.