Project 3: Tumor-associated biomarkers for HIV-associated Diffuse Large B-cell Lymphoma in Malawi and South Africa

摘要：项目3：HIV相关弥漫性大B细胞的肿瘤相关生物标志物 马拉维和南非的淋巴瘤 由于艾滋病毒感染的流行水平，撒哈拉以南非洲（SSA）的淋巴瘤发病率正在增加， 人口增长和老龄化。弥漫性大B细胞淋巴瘤（DLBCL）与HIV高度相关， HIV感染者中最常见的淋巴瘤亚型，也是癌症死亡的最常见原因 在高收入国家（HIC）的艾滋病毒感染者中。尽管组织学上相似的外观，艾滋病毒- 相关DLBCL与免疫活性人群中的DLBCL在生物学上不同， HIV感染人群取决于其发生的HIV免疫学和病毒学环境。 然而，目前的诊断，危险分层和治疗不能解释这些差异， 不完全理解，并且克服这些挑战的合适的患者队列在历史上一直是 缺乏我们的长期目标是通过应用有前景的治疗方案来改善SSA中HIV相关DLBCL的结局。 区域产生的生物标志物，建立在我们以前的免疫表型和分子分析， 来自该地区的DLBCL，在马拉维和南非的患者的前瞻性队列。这项工作将进一步 表征影响整个HIV谱的肿瘤生物学的肿瘤微环境因素- 相关的免疫功能障碍。我们假设可以识别预后生物标志物， 在撒哈拉以南非洲地区实施，以更好地为这一具有挑战性和脆弱的人口量身定制治疗。鉴于 由于该地区普遍存在艾滋病毒流行，根据艾滋病毒状况对特定肿瘤类型进行了比较， 在这种情况下是唯一可能的。在美国进行类似的研究具有挑战性，因为艾滋病毒感染者相对较少， 阳性癌症，以及HIV感染和一般HIV阴性美国人群之间的差异， 年龄，以及行为和其他癌症风险因素。这些努力将得到加强， 与生物信息学和测序核心设施建立了合作，使拟议的研究能够 产生见解，为全球HIV相关DLBCL的护理提供信息。拟议的工作是必要的， 了解淋巴瘤发生的生物学因素，提高HIV相关DLBCL的生存率 在高收入和低收入国家。

ABSTRACT: PROJECT 3: Tumor-associated biomarkers for HIV-associated Diffuse Large B-cell Lymphoma in Malawi and South Africa Lymphoma incidence in sub-Saharan Africa (SSA) is increasing due to epidemic levels of HIV infection, population growth, and aging. Diffuse large B-cell lymphoma (DLBCL) is highly associated with HIV, the commonest lymphoma subtype among HIV-infected individuals, and the commonest cause of cancer death among people living with HIV in high-income countries (HIC). Despite histologically similar appearances, HIV- associated DLBCL differs biologically from DLBCL in immunocompetent populations and may also differ within HIV-infected populations depending on the HIV immunologic and virologic environment in which they occur. However, current diagnosis, risk stratification and therapy do not account for these differences which remain incompletely understood, and suitable patient cohorts to overcome these challenges have historically been lacking. Our long-term goal is to improve outcomes for HIV-associated DLBCL in SSA by applying promising regionally generated biomarkers, building on our previous immunophenotypic and molecular analyses of DLBCL from the region, to a prospective cohort of patients in Malawi and South Africa. The work will further characterize tumor microenvironmental factors that influence tumor biology across the spectrum of HIV- associated immune dysfunction. We hypothesize that prognostic biomarkers can be identified and implemented in SSA to better tailor treatment for this challenging and vulnerable population. Given the generalized HIV epidemic in the region, comparisons within specific tumor types based on HIV status are uniquely possible in this setting. Similar studies are challenging to conduct in the US, given relatively few HIV- positive cancers, and differences between the HIV-infected and general HIV-negative US population with respect to age, as well as behavioral and other cancer risk factors. These efforts will be enhanced by established collaborations with bioinformatics and sequencing core facilities, allowing the proposed research to yield insights which inform the care of HIV-associated DLBCL worldwide. The proposed work is necessary to understand the biological factors underlying lymphomagenesis and improve survival for HIV-associated DLBCL in high- and low-income countries.