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.

项目总结/文摘