Genomic and Microenvironment Analysis of HIV-Associated Diffuse Large B-cell Lymphoma (Immuno/Microenvironment)

HIV 相关弥漫性大 B 细胞淋巴瘤的基因组和微环境分析（免疫/微环境）

• 批准号: 10620074
• 负责人: STEVEN Terry ROSEN
• 金额: $ 25万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10620074
• 关键词: Address; Area; Automobile Driving; BCL2 gene; BCL6 gene; Cause of Death; Cells; Classification; Collaborations; Data; Disease; Epstein-Barr Virus Infections; Evaluation; Future; Gene Expression; Gene Expression Profiling; Genomics; HIV; HIV Seronegativity; Human Herpesvirus 4; Immunofluorescence Immunologic; Inflammatory; Integration Host Factors; Lymphoma; Lymphomagenesis; Methylation; Molecular; Molecular Profiling; Mutation; Non-Hodgkin' s Lymphoma; Pathogenesis; Pathology; Pathway interactions; Patients; Persons; Play; Prognosis; Research Personnel; Resources; Role; Shapes; Therapeutic; antiretroviral therapy; bioinformatics pipeline; co-infection; comorbidity; design; exome sequencing; genomic data; insight; large cell Diffuse non-Hodgkin' s lymphoma; leukemia/lymphoma; multiple omics; novel therapeutics; programmed cell death ligand 1; searchable database; targeted therapy trials; transcriptome; tumor; tumor microenvironment

PROJECT SUMMARY/ABSTRACT This proposal addresses the high priority statement related to “HIV-associated comorbidities, coinfections, and complications.” This study will be addressing this high priority requirement from two aspects, including the study of co-infection by EBV and HIV, as well as the molecular differences between EBV+ and EBV- diffuse large B- cell lymphoma in HIV+ patients. HIV-associated diffuse large B-cell lymphoma (HIV+/DLBCL) remains an understudied disease and is one of the leading causes of death in persons living with HIV on anti-retroviral therapy. Although there have been significant strides taken with de novo DLBCL in terms of molecular classification, HIV+/DLBCL has lagged behind, particularly because it was originally excluded from most large studies. While approximately 30% of these tumors can be EBV-positive, potentially serving as a driving mechanism for lymphomagenesis, the molecular pathogenesis in the majority of cases have not been comprehensively studied. Additionally, the tumor microenvironment (TME) plays an important role in lymphomas related to prognosis and therapy, but this area has not been investigated in HIV+/DLBCL. We hypothesize that by investigating the genomic landscape and TME of HIV+/DLBCL, we will identify key cellular vulnerabilities and pathways that can provide insights for tailoring novel therapies for patients with HIV+/EBV-positive versus HIV+/EBV-negative DLBCL. Utilizing our multi-institutional collaboration, we plan to evaluate the 1) whole “omics” of HIV+/DLBCL as well as 2) investigate the TME of HIV+/DLBCL using multispectral immunofluorescence in conjunction with spatial gene expression data, EBV-status, and genomic data. 3) We will utilize the Lymphoma and Leukemia Molecular Profiling Project (LLMPP) with their established pathology review and bioinformatics pipeline to facilitate this study which will generate important data that we and other investigators around the world can use in future years to generate new hypothesis, design targeted treatments and trials for this aggressive disease.

项目概要/摘要 该提案涉及与“艾滋病毒相关合并症、合并感染和 这项研究将从两个方面解决这一高度优先的要求，包括研究。 EBV 和 HIV 合并感染的情况，以及 EBV+ 和 EBV- 之间的分子差异 弥漫性大 B- HIV+患者的细胞淋巴瘤。 HIV 相关的弥漫性大 B 细胞淋巴瘤 (HIV+/DLBCL) 仍然是一种尚未得到充分研究的疾病，并且是最常见的疾病之一 艾滋病毒感染者接受抗逆转录病毒治疗时死亡的主要原因。 新发 DLBCL 在分子分类方面取得了长足进步，HIV+/DLBCL 已经落后， 特别是因为它最初被排除在大多数大型研究之外，而大约 30% 的肿瘤。 可能是 EBV 阳性，可能作为淋巴瘤发生的驱动机制，分子 另外，大多数病例的发病机制尚未得到全面研究。 微环境（TME）在与预后和治疗相关的淋巴瘤中发挥着重要作用，但该领域 尚未在 HIV+/DLBCL 中进行过研究，我们通过研究基因组图谱对此进行了调查。 HIV+/DLBCL 的 TME，我们将确定关键的细胞脆弱性和途径，为治疗提供见解 利用我们的技术为 HIV+/EBV 阳性和 HIV+/EBV 阴性 DLBCL 患者量身定制新疗法。 通过多机构合作，我们计划评估 1) HIV+/DLBCL 的整个“组学”以及 2) 调查 使用多光谱免疫荧光结合空间基因表达对 HIV+/DLBCL 进行 TME 数据、EBV 状态和基因组数据 3) 我们将利用淋巴瘤和白血病分子分析项目。 （LLMPP）及其已建立的病理学审查和生物信息学管道来促进这项研究，这将 生成我们和世界各地的其他研究人员可以在未来几年使用的重要数据 新的假设，针对这种侵袭性疾病设计有针对性的治疗方法和试验。