The interplay of social and molecular determinants in lung cancer disparity

肺癌差异中社会和分子决定因素的相互作用

基本信息

批准号：
10364112
负责人：
Brian M. Rivers
金额：
$ 58.93万
依托单位：
MOREHOUSE SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2027-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10364112
关键词：
Address Affect African American population American Apoptosis Aspirate substance Behavioral Sciences Bioinformatics Biologic Characteristic Biological Biological Factors Biological Markers Biometry Biopsy Blood Bronchoscopy CCL20 gene Cancer Biology Cancer Patient Cancer cell line Caring Cell Line Cell Proliferation Cells Censuses Characteristics Chronic stress Cigarette Classification Clinical Trials Code Computer software Consent Consumption Data Data Analyses Diagnosis Disease Disease Outcome Enrollment Enzyme-Linked Immunosorbent Assay Ethnic group European Evidence based intervention Gender Gene Expression Profiling Goals Hospitals Hydrocortisone Immune Immune system Immunity Immunologics Immunophenotyping Immunotherapy Incidence Individual Interdisciplinary Study Investigational Drugs Knowledge Ligands Link Lung Lung Neoplasms Malignant Neoplasms Malignant neoplasm of lung Mediating Metabolic Metabolism Methods Molecular National Institute on Minority Health and Health Disparities Neighborhoods Nodal Non-Small-Cell Lung Carcinoma Oncology Outcome Pathology Pathway interactions Patients Phenotype Physiology Prognosis Prognostic Marker Proteins Public Health Race Research Risk Risk Factors Role Saliva Sampling Serum Shapes Smoking Social Characteristics Socioeconomic Status Stress Supporting Cell The Cancer Genome Atlas Tissues Tumor Immunity Tumor Tissue Tumor stage Tumor-infiltrating immune cells Visit Work base beta-Chemokines cancer health disparity cancer immunobiology cancer therapy chemokine chemokine receptor cohort design detection method disparity reduction effective therapy ethnic disparity evidence base improved lung cancer cell mortality multidisciplinary patient stratification patient subsets peripheral blood racial difference racial disparity recruit social social factors social interventions social stress stemness success targeted treatment therapeutic biomarker therapeutic target therapy outcome trait transcriptome treatment response tumor

Address Affect African American population American Apoptosis Aspirate substance Behavioral Sciences Bioinformatics Biologic Characteristic Biological Biological Factors Biological Markers Biometry Biopsy Blood Bronchoscopy CCL20 gene Cancer Biology Cancer Patient Cancer cell line Caring Cell Line Cell Proliferation Cells Censuses Characteristics Chronic stress Cigarette Classification Clinical Trials Code Computer software Consent Consumption Data Data Analyses Diagnosis Disease Disease Outcome Enrollment Enzyme-Linked Immunosorbent Assay Ethnic group European Evidence based intervention Gender Gene Expression Profiling Goals Hospitals Hydrocortisone Immune Immune system Immunity Immunologics Immunophenotyping Immunotherapy Incidence Individual Interdisciplinary Study Investigational Drugs Knowledge Ligands Link Lung Lung Neoplasms Malignant Neoplasms Malignant neoplasm of lung Mediating Metabolic Metabolism Methods Molecular National Institute on Minority Health and Health Disparities Neighborhoods Nodal Non-Small-Cell Lung Carcinoma Oncology Outcome Pathology Pathway interactions Patients Phenotype Physiology Prognosis Prognostic Marker Proteins Public Health Race Research Risk Risk Factors Role Saliva Sampling Serum Shapes Smoking Social Characteristics Socioeconomic Status Stress Supporting Cell The Cancer Genome Atlas Tissues Tumor Immunity Tumor Tissue Tumor stage Tumor-infiltrating immune cells Visit Work base beta-Chemokines cancer health disparity cancer immunobiology cancer therapy chemokine chemokine receptor cohort design detection method disparity reduction effective therapy ethnic disparity evidence base improved lung cancer cell mortality multidisciplinary patient stratification patient subsets peripheral blood racial difference racial disparity recruit social social factors social interventions social stress stemness success targeted treatment therapeutic biomarker therapeutic target therapy outcome trait transcriptome treatment response tumor

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项目摘要

Abstract African Americans (AAs) are disproportionally affected by lung cancer, compared with all other racial and ethnic groups in terms of incidence and survival. Disproportionate diagnosis of aggressive disease and poor survival among AAs highlights the critical need for further studies that characterize racial differences in lung cancer. Our goal is to address this vital knowledge gap by identifying molecular, biological, and social characteristics (neighborhood-level factors) underlying the disease’s aggressiveness, thereby reducing the disparity between African Americans (AAs) and European Americans (EAs). Our central hypothesis is that CC chemokine receptor-6 (CCR6) and its only natural ligand CCL20 add to the racial difference in molecular footprint and immune landscape, impacting racial disparity in lung cancer aggressiveness and prognosis. In addition to these biological factors, social factors associated with chronic stress, which elevated cortisol, shape the immunological landscape differently in AAs, contributing to racial differences in aggressiveness and prognosis. There is a unique possibility that CCR6/CCL20 and social characteristics contribute to the disparity in lung cancer among AAs, which has never been explored. Hence the proposed work will enhance understanding of cell biological traits of aggressive lung cancers, particularly non-small cell lung cancer (NSCLC), which accounts for ~85% of the lung cancers that underlie ethnic disparities in disease outcomes and mechanisms by which cells acquire aggressive phenotypes. To accomplish these goals, we have assembled a multidisciplinary research team with complementary expertise in cancer immuno-biology, oncology, pulmonary care, pathology, public health/behavioral science, bioinformatics, and biostatistics to investigate the following aims: A1. Establish the association of CCR6-CCL20 axis in NSCLC aggressiveness and therapeutic response among AAs and EAs; A2. Ascertain the race-specific differences in the immunological landscape contributing to the NSCLC disparity and A 3. Determine the impact of social stress on the immune signature among AA and EA NSCLC patients. Completion of these aims will i) inform a rapid, non-invasive chemokine based detection methods which will allow classifying potentially fatal lung cancers, ii) a method for early patient stratification so that risk-adapted chemokine-based therapies can be designed to match patient subgroups with distinct CCR6 profiles, iii) to offer more effective treatment approach, iv) a framework for improving the success rate of clinical trials involving investigational drugs by establishing new criteria for patient classification, Immune-based strategies to reduce disparity and, v) identify geospatial neighborhood characteristics impacting the immune system and outcome in lung cancer aggressiveness and therapeutic outcome on which evidence-based intervention can be developed to address the disparity in lung cancer.

与所有其他种族相比在发生率和生存方面。侵略性疾病和差的诊断不成比例 AAS之间的生存强调了对肺部种族差异的进一步研究的关键需求癌症。我们的目标是通过识别分子，生物学和社会来解决这一重要知识差距该疾病侵略性的特征（邻里级别因素），从而降低了非洲裔美国人（AAS）与欧洲美国人（EAS）之间的差异。我们的中心假设是CC 趋化因子受体-6（CCR6）及其唯一的天然配体CCL20增加了分子足迹的种族差异和免疫景观，影响肺癌侵略性和预后的种族差异。此外这些生物学因素，与慢性压力相关的社会因素，这些因素升高皮质醇，塑造 AAS的免疫学景观不同，导致侵略性和预后的种族差异。 CCR6/CCL20和社会特征有可能导致肺癌差异在从未探索过的AAS中。因此，拟议的工作将增强对细胞的理解侵略性肺癌的生物学特征，尤其是非小细胞肺癌（NSCLC）的生物学特征〜85％的肺癌是疾病结局和机制中种族差异的基础的肺癌获得侵略性表型。为了实现这些目标，我们组装了一项多学科研究团队具有癌症免疫生物学，肿瘤学，肺部护理，病理学，公众的完整专业知识健康/行为科学，生物信息学和生物统计学以研究以下目的：A1。建立 AAS和EAS之间NSCLC侵略性和治疗反应中CCR6-CCL20轴的关联； A2。确定有助于NSCLC差异的免疫景观中特定种族的差异 A 3。确定社会压力对AA和EA NSCLC患者中免疫特征的影响。这些目的的完成i）i）为一种基于快速的，非侵入性趋化因子的检测方法提供信息允许对潜在的致命肺癌进行分类，ii）一种早期患者分层的方法可以设计基于趋化因子的疗法以与患者亚组具有不同的CCR6概况，iii）提供更有效的治疗方法，iv）提高临床试验成功率的框架通过建立针对患者分类的新标准，基于免疫的策略来减少研究药物差异和，v）确定影响免疫系统和结果的地理空间邻里特征肺癌的侵略性和治疗结果可以开发基于证据的干预措施解决肺癌的差异。