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

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:
$25.0万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-09-01 至 2022-11-30

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中文摘要
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英文摘要
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.
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国内基金
海外基金
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