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

项目 3：马拉维和南非 HIV 相关弥漫性大 B 细胞淋巴瘤的肿瘤相关生物标志物

• 批准号: 10238162
• 负责人: Yuri Fedoriw
• 金额: $ 23.24万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-13 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10238162
• 关键词: AIDS-Related Lymphoma; Achievement; Africa South of the Sahara; Age; Aging; Appearance; Behavioral; Bioinformatics; Biological; Biological Factors; Biological Markers; Cancer Etiology; Caring; Cessation of life; Characteristics; Clinical; Clinical Research; Clinical Trials Design; Cohort Studies; Collaborations; Core Facility; Country; DNA Sequencing Facility; Data; Diagnosis; Environment; Epidemic; Future; Gene Expression; Genes; Genomics; Goals; HIV; HIV Infections; HIV Seronegativity; HIV Seropositivity; Histologic; Hospitals; Immune; Immune System Diseases; Immunocompetent; Immunogenomics; Immunologics; Incidence; Income; Individual; Inflammatory; Infrastructure; Kaposi Sarcoma; Lymphoma; Lymphomagenesis; Malawi; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Molecular; Molecular Analysis; Newly Diagnosed; Outcome; Patient-Focused Outcomes; Patients; Pattern; Population; Population Growth; Prognosis; Prognostic Marker; Prospective cohort; Regional Disease; Research; Resources; Risk Factors; Site; South Africa; Speed; Tissue Sample; Translational Research; Tumor Biology; Universities; Vulnerable Populations; Work; advanced analytics; base; cancer risk; chemotherapy; clinical diagnostics; clinical remission; cohort; comparison group; differential expression; experience; improved; improved outcome; individualized medicine; innovation; insight; large cell Diffuse non-Hodgkin' s lymphoma; low income country; prognostic; prospective; response; risk stratification; routine care; scale up; screening; sociodemographic factors; specific biomarkers; transcriptome; transcriptome sequencing; tumor; tumor microenvironment; tumor-immune system interactions; virology

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.

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，撒哈拉以南非洲地区（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 高收入国家 (HIC) 的艾滋病毒感染者。尽管组织学外观相似，但 HIV- 相关的 DLBCL 在生物学上与免疫功能正常人群中的 DLBCL 不同，并且也可能在以下方面有所不同： HIV 感染人群取决于其所在的 HIV 免疫学和病毒学环境。 然而，当前的诊断、风险分层和治疗并没有考虑到这些差异，这些差异仍然存在 尚未完全了解，并且历史上一直存在克服这些挑战的合适患者群体 缺乏。我们的长期目标是通过应用有前景的药物来改善 SSA 中 HIV 相关 DLBCL 的治疗结果 基于我们之前的免疫表型和分子分析，区域生成的生物标志物 来自该地区的 DLBCL 被纳入马拉维和南非的前瞻性患者队列。这项工作将进一步 描述影响整个 HIV 谱系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并 在 SSA 中实施，以便更好地针对这一具有挑战性的弱势群体制定治疗方案。鉴于 该地区普遍的艾滋病毒流行情况，根据艾滋病毒状况对特定肿瘤类型进行比较 在这种情况下是独一无二的。鉴于相对较少的艾滋病毒感染者，在美国进行类似的研究具有挑战性。 阳性癌症，以及艾滋病毒感染者和普通艾滋病毒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 产生的见解可为全球艾滋病毒相关 DLBCL 的护理提供参考。拟议的工作是必要的 了解淋巴瘤发生的生物学因素并提高 HIV 相关 DLBCL 的生存率 在高收入和低收入国家。