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

摘要：总体来说。爱荷华大学/梅奥诊所淋巴瘤孢子(孢子)是一个动态的， 以两个综合性癌症中心为基础的富有成效的转化型癌症研究计划，这是第一个 2002年获得资金，并于2007年和2012年以竞争性方式续签。是持续取得成功的核心 孢子是爱荷华州和梅奥的研究人员之间的协作互动，以及孢子基础 实验室、临床和人口科学研究人员将重点放在淋巴瘤上。孢子的总体目标 是支持创新的、互动的、严格的翻译淋巴瘤研究，该研究利用 这两个机构的实验室、临床和人口科学专业知识。在上一个资助期内， 新的肿瘤标志物和预后的鉴定表明，孢子的产量很高 临床上使用的指数；科学发现，导致了创新的临床试验 孢子之外；多份出版物，其中许多是由两个机构的调查人员撰写的；以及 转化性临床试验的应计费用。孢子参与了垂直和水平的多重生产 与其他国家和国际学术机构和组织的合作。例如， 基于孢子的UI/MC分子流行病学资源是这两种孢子研究的重要资源 以及由其他拨款支持的研究项目。它是资助淋巴瘤的基金会 结果流行病学(LEO)队列(U01 CA195568)，包括另外6个机构，从而 加强孢子促进的研究的范围和多样性。目前的建议包括4个主要方面 研究项目。虽然所有的项目都是新的，但它们都是基于过去获得的研究成果 资助期。项目1将调查为什么先天免疫系统(单核/巨噬细胞) 在淋巴瘤中被抑制，目的是在I期试验中用一种新型的Sirpα-FC来克服这种抑制。 项目2的重点是通过改变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，并与抗PD1治疗联合应用 NHL的。项目3正在研究调节信号通路(TRAF3和GSK3)的失调 侵袭性淋巴瘤患者的葡萄糖高代谢。他们将在I期试验中测试一种新型的GSK3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。 基因组生物标记物、肿瘤基因表达和临床因素在诊断时预测 接受免疫化疗的FL患者会出现早期的临床失败。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分别通过该计划。最后，孢子会增强 通过共享核心支持两个机构的转化性淋巴瘤研究的基础设施 管理、生物统计学和生物信息学、生物谱学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.