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; 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.

项目摘要/摘要 该提案涉及与“与HIV相关的合并症，共同感染和 并发症。”这项研究将从两个方面解决这一高优先级要求，包括研究 EBV和HIV共同感染，以及EBV+和EBV-散射大B-之间的分子差异 HIV+患者的细胞淋巴瘤。 与HIV相关的扩散大B细胞淋巴瘤（HIV+/DLBCL）仍然是一种理解的疾病，是 抗逆转录病毒疗法的HIV患者的主要死亡原因。虽然有重要的 在分子分类方面，从头dlbcl进行的大步前进，HIV+/DLBCL落后于 特别是因为它最初被排除在大多数大型研究之外。这些肿瘤中约有30％ 可以是EBV阳性的，有可能用作淋巴作用的驱动机制，分子 大多数病例的发病机理尚未全面研究。另外，肿瘤 微环境（TME）在与预后和治疗有关的淋巴瘤中起重要作用，但是该区域 尚未在HIV+/DLBCL中进行研究。我们通过研究基因组景观和 HIV+/DLBCL的TME，我们将确定可以为您提供见解的关键蜂窝漏洞和途径 针对HIV+/EBV阳性患者与HIV+/EBV阴性DLBCL的患者调整新疗法。利用我们的 多机构合作，我们计划评估1）HIV+/DLBCL的整个“ OMICS”以及2）调查 HIV+/DLBCL的TME使用多光谱免疫荧光与空间基因表达结合 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）及其既定的病理综述和生物信息学管道，以促进这项研究 生成我们和世界各地其他调查人员在未来几年中可以使用的重要数据来生成 新的假设为这种侵略性疾病设计了有针对性的治疗和试验。