Host factors, tumor microenvironment and survival in a multiethnic study of Hodgkin lymphoma patients

霍奇金淋巴瘤患者多种族研究中的宿主因素、肿瘤微环境和生存

基本信息

批准号：
9924449
负责人：
Wendy Cozen
金额：
$ 20.18万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-15 至 2020-10-18
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9924449
关键词：
Address Admixture Adolescent and Young Adult Affect African American Age Anatomy Asians B-Lymphocytes Biological Markers Biology Biopsy CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes California Cancer Center Cells Cellularity Cessation of life Characteristics Child Childhood Cities Clinical Clinical Data County DNA Dendritic Cells Diagnosis Diagnostic Disease Economic Development Elderly Epidemiology Ethnic Origin Ethnic group Etiology European Excess Mortality FOXP3 gene Flowers Formalin Frequencies GATA3 gene Gene Expression Gene Expression Profile Gene Expression Profiling Genetic Granzyme Heart Diseases Hispanics Histology Hodgkin Disease Hospitals Human Herpesvirus 4 Immune Immunobiology Immunohistochemistry Incidence Integration Host Factors Knowledge Late Effects Leukocytes Los Angeles Lung diseases Lymphocyte Lymphoma MS4A1 gene Malignant Neoplasms Measures Mediating Medical center Methodology Morbidity - disease rate Non-Malignant Not Hispanic or Latino Outcome Paraffin Embedding Pathologic Pathology Patients Pattern Population Predisposition Progression-Free Survivals Progressive Disease Race Recurrent disease Reed-Sternberg Cells Regulatory T-Lymphocyte Reporting Risk Risk stratification Sample Size Sclerosis Second Primary Cancers Socioeconomic Status Stage at Diagnosis Subgroup Suggestion Survivors Symptoms T-Lymphocyte T-Lymphocyte Subsets Testing Tissue Microarray Tumor Tissue Universities University of Southern California Norris Cancer Center Western World age group aggressive therapy base biomarker development cancer cell clinical biomarkers clinical center design disorder subtype eosinophil ethnic diversity experience hazard improved macrophage mast cell medical schools mortality multidisciplinary nano-string neoplastic neoplastic cell novel therapeutic intervention outcome prediction patient response predictive signature prognostic public health relevance racial and ethnic relapse prediction sex socioeconomics survival prediction treatment response tumor tumor microenvironment young adult

项目摘要

DESCRIPTION (provided by applicant): Classical Hodgkin lymphoma (cHL) is the most common form of lymphoma affecting people under the age of 30 in the Western World. Treatment responses after initial therapies are excellent in young people, however late effects cause considerable mortality and morbidity. 25- 30% of patients experience relapse or progressive disease following initial treatment and 5-15% die of their disease within 10 years. An improved understanding of the pathobiology of cHL is an essential requirement for biomarker development and novel therapeutic approaches to improve initial and late outcomes. cHL is unique among cancers in that the malignant cells comprise less than 1% of the tumor with the remainder of the tumor microenvironment (TME) composed of a variety of immune cells. We have shown that in some populations, the composition of the TME affects cHL outcome. Here we will examine the correlation between the TME composition and survival in cHL across, age, sex, EBV status, histology and racial/ethnic groups (Aim 1). We will also examine the effect of host factors (age, sex, race/ethnicity, SES), EBV status and histology on TME composition (Aim 2) and we will conduct analyses to determine whether TME mediates or interacts with host factors to impact survival (Aim 3). This will be the largest study of cHL TME conducted to date and the only one designed to specifically examine relationships in different racial/ethnic and age groups. To conduct this study, we have assembled a multidisciplinary team of experts. We will perform gene expression profiling (our validated Scott Predictor) using NanoString and we will examine specific T-cell and other subsets, including macrophages and B-cells, implicated in outcome, using immunohistochemistry on formalin-fixed paraffin-embedded diagnostic biopsies from 2,688 U.S. multiethnic cHL patients from 5 large clinical centers. EBV DNA in the tumor cells will also be measured. Tissue microarrays will be constructed and immunohistochemistry automatically scored. We will also collect demographic and clinical data including age, race/ethnicity, sex, socioeconomic status, treatment, progression-free and overall survival, B symptoms, anatomic site, stage and other information. With this sample size, the minimum detectable Hazard Ratio (HR) with 80% power is 1.55 to 1.32 for a TME binary variable with frequency ranging from 0.1 to 0.5, respectively. The ranges of detectable marginal HR are well-within the range of previously observed effects and should enable us to test marginal effects by race/ethnicity, age and other factors. The significance of this proposal lies in identifying population differences for a cutting-edge clinical biomarker and elucidating the immunobiology of the TME in different demographic groups.

描述（由适用提供）：经典的霍奇金淋巴瘤（CHL）是影响西方世界30岁以下人们的最常见淋巴瘤形式。初始疗法后的治疗反应在年轻人中非常出色，但是较晚的效果会导致可考虑的死亡率和发病率。初次治疗后，有25-30％的患者在10年内经历了救济或进行性疾病。对CHL病理生物学的了解是生物标志物发育和新型治疗方法以改善初始和晚期结局的必不可少的要求。 CHL在癌症中是独一无二的，因为恶性细胞不到肿瘤的1％，其余的肿瘤微环境（TME）由多种免疫细胞组成。我们已经表明，在某些人群中，TME的组成会影响CHL结果。在这里，我们将研究CHL的TME组成与年龄，性别，EBV状态，组织学和种族/种族/种族群体之间的相关性（AIM 1）。我们还将检查宿主因素（年龄，性别，种族/种族，SES），EBV状态和组织学对TME组成的影响（AIM 2），我们将进行分析以确定TME是否介导或与宿主因素相互作用以影响生存率（AIM 3）。这将是迄今为止进行的CHL TME的最大研究，也是唯一旨在专门研究不同种族/种族和年龄段的关系的研究。为了进行这项研究，我们组建了一个多学科的专家团队。我们将使用纳米链接进行基因表达谱分析（我们经过验证的SCOTT预测器），我们将使用福尔马林固定的帕诺夫蛋白膜膜片的免疫组织化学来检查结果，包括巨噬细胞和B细胞，包括巨噬细胞和B细胞，这暗示了2,688 U.S. U.S. U.S. Multiacted诊断的生存。还将测量肿瘤细胞中的EBV DNA。将构建组织微阵列并自动评分免疫组织化学。我们还将收集人口统计学和临床数据，包括年龄，种族/种族，性别，性别，社会经济状况，治疗，无进展和整体生存，B症状，解剖部位，阶段和其他信息。对于此样本量，对于TME二进制变量，频率范围分别为0.1至0.5的最小可检测危险比（HR）为1.55至1.32。可检测到的边缘人力资源的范围与以前观察到的效果的范围很好，并应使我们能够通过种族/种族，年龄和其他因素来测试边际影响。该提案的意义在于确定尖端临床生物标志物的人口差异，并阐明不同人口组中TME的免疫生物学。