Lymphoma Specialized Program of Research Excellence (SPORE) in Human Cancer

摘要：总体而言。爱荷华州大学/马约诊所淋巴瘤孢子（孢子）是一个动态的， 生产，转化癌症研究计划的基础上，两个综合癌症中心，是第一个 2002年获得资助，2007年和2012年竞争性续延。在不断取得成功的中心， SPORE是爱荷华州和马约的研究人员之间的协作互动，以及SPORE基本 实验室、临床和人口科学研究人员专注于淋巴瘤。SPORE的总体目标 是支持创新，互动，严格的转化淋巴瘤研究，利用专业知识， 实验室、临床和人口科学专业知识。在上一个资助期内， 通过鉴定新的肿瘤标志物和预后评估， 正在临床上使用的指数;导致创新性临床试验的科学发现， 在SPORE之外;多个出版物，其中许多由来自两个机构的研究人员撰写;以及活跃的 转化临床试验的累积。SPORE涉及多个生产性纵向和横向 与其他国家和国际学术机构和组织的合作。比如说 基于SPORE的UI/MC分子流行病学资源是SPORE研究的重要资源 及其他赠款的研究项目。它作为淋巴瘤的资金基础 结局流行病学（LEO）队列（U 01 CA 195568），包括另外6家机构，因此 扩大由SPORE促进的研究的范围和多样性。目前的建议包括4个主要 研究项目。虽然所有项目都是新的，但它们都是基于过去取得的研究成果 融资期。项目1将研究为什么先天免疫系统（单核细胞/巨噬细胞） 在淋巴瘤中抑制，并旨在在I期试验中用新型SIRPα-Fc克服这种抑制。 项目2的重点是通过修改淋巴瘤微环境来增强临床T细胞反应， 增强抗原释放、抗原呈递和T细胞活化，并将其与抗PD 1疗法组合 关于NHL项目3正在研究调节细胞凋亡的信号通路（TRAF 3和GSK 3）， 侵袭性淋巴瘤的葡萄糖高代谢他们将在I期试验中测试一种新的GSK 3抑制剂。 项目4是一个人口科学项目，将测试生殖系（宿主）和体细胞（肿瘤）的组合。 基因组生物标志物，肿瘤基因表达和临床因素，以预测诊断， 免疫化疗治疗的FL患者将具有早期临床失败。该孢子还包括 发展研究和职业提升计划，以追求新的翻译概念， 淋巴瘤研究和新的研究人员通过该计划分别。最后，SPORE将增强 通过共享核心支持两个机构的转化淋巴瘤研究的基础设施 管理、生物统计学和生物信息学、生物标本和临床研究方面的资源。

ABSTRACT: Overall. The University of Iowa/Mayo Clinic Lymphoma SPORE (SPORE) is a dynamic, productive, translational cancer research program based at two comprehensive cancer centers that was first funded in 2002 and competitively renewed in 2007 and 2012. At the center of the ongoing success of the SPORE is the collaborative interaction between investigators at Iowa and Mayo, as well as SPORE basic laboratory, clinical and population science investigators focused on lymphoma. The overall goal of the SPORE is to support innovative, interactive, rigorous translational lymphoma research that leverages the expertise of laboratory, clinical and population science expertise at both institutions. Over the last funding period, the SPORE has been highly productive as demonstrated by identification of new tumor markers and prognostic indices that are being used clinically; scientific findings that led to innovative clinical trials both within and outside the SPORE; multiple publications with many authored by investigators from both institutions; and brisk accrual to translational clinical trials. The SPORE was involved in multiple productive vertical and horizontal collaborations with other national and international academic institutions and organizations. For example, the UI/MC Molecular Epidemiology Resource based in the SPORE is a vital resource for both SPORE research and research projects supported by other grants. It served as the foundation for the funding of the Lymphoma Epidemiology of Outcomes (LEO) Cohort (U01 CA195568) that includes 6 additional institutions, thereby enhancing the scope and diversity of research facilitated by the SPORE. The current proposal includes 4 major research projects. While all of the projects are new, they are based on research results obtained over the past funding period. Project 1 will investigate why the innate immune system (monocyte/macrophage) is suppressed in lymphoma and aims to overcome that suppression with a novel SIRPα-Fc in a phase I trial. Project 2 focuses on enhancing the clinical T-cell response by modifying the lymphoma microenvironment to augment antigen release, presentation of antigen, and T cell activation and combining it with anti-PD1 therapy of NHL. Project 3 is investigating the dysregulated signaling pathways (TRAF3 and GSK3) that regulate glucose hypermetabolism in aggressive lymphoma. They will test a novel GSK3 inhibitor in a phase I trial. Project 4 is a Population Science project will test a combination of germline (host) and somatic (tumor) genomic biomarkers, tumor gene expression, and clinical factors to predict at diagnosis which immunochemotherapy-treated FL patients will have an early clinical failure. The SPORE also includes Developmental Research and Career Enhancement Programs to pursue novel translational concepts in lymphoma research and new investigators through the programs respectively. Finally, the SPORE will enhance the infrastructure that supports translational lymphoma research at both institutions through shared core resources in Administration, Biostatistics and Bioinformatics, Biospecimens, and Clinical Research.