Project 1-Immunogenomic diversity in triple negative breast cancer health disparities

项目 1-三阴性乳腺癌健康差异中的免疫基因组多样性

• 批准号: 10005253
• 负责人: Lucio Miele
• 金额: $ 22.29万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-19 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005253
• 关键词: 5' -Nucleotidase; Address; Adenosine; Adjuvant Chemotherapy; Affect; African American; Aftercare; American; Biological Markers; Biopsy; Breast Cancer Patient; CD3 Antigens; Cancer Biology; Cells; Chronic; Clinical; Data; Development; Diagnostic; Disease; Disease remission; Epigenetic Process; European; Event; Fatty Acids; Foundations; Future; Gene Expression; Genes; Genetic; Genomics; Grant; High Risk Woman; Histologic; Immune; Immunogenomics; Immunologic Markers; Immunologics; Immunotherapy; Impairment; Incidence; Inflammation; Inflammatory; Inflammatory Infiltrate; Ligands; Link; Literature; Louisiana; Measurable; Molecular; Molecular Profiling; Monoclonal Antibodies; Mutation; Myeloid-derived suppressor cells; Neoadjuvant Therapy; Non obese; Obesity; Obesity Epidemic; Outcome; Pathologic; Patient Self-Report; Patients; Plasma; Population; Portraits; Postoperative Period; Premenopause; Prevention strategy; Race; Reporting; Role; Sampling; Somatic Mutation; Spatial Distribution; Stage at Diagnosis; T cell response; T-Lymphocyte; Testing; Therapeutic; Transcript; Tumor Immunity; Tumor Markers; Tumor stage; Tumor-Infiltrating Lymphocytes; Tumor-infiltrating immune cells; Woman; base; cancer health disparity; chemotherapy; clinical practice; clinically actionable; comorbidity; health disparity; high risk; molecular subtypes; monocyte; notch protein; novel; obesity risk; outcome forecast; patient population; personalized immunotherapy; precision medicine; predicting response; predictive signature; prognostic; prospective; response; therapeutic target; therapy outcome; therapy resistant; transcriptome; transcriptome sequencing; treatment optimization; triple-negative invasive breast carcinoma; tumor; tumor microenvironment; tumor progression

ABSTRACT- Project 1 The incidence of triple-negative breast cancer (TNBC) in Louisiana is among the highest in the nation, particularly among African American (AA) women. AA women are also at high risk of obesity compared to European-American (EA). These apparently separate conditions may be linked by genetics, epigenetics and chronic inflammation. TNBC is a genetically heterogeneous group of diseases that includes multiple molecular subtypes based on transcript expression and somatic mutations. These subtypes respond differently to standard chemotherapy but are not yet routinely in clinical practice and it is unknown how well they apply to AA patients. Our preliminary data and the literature show that molecular signatures as well as inflammatory cells and T cells infiltrating TNBC may provide important prognostic information. As a part of this P20 Planning Grant project, we will explore the relationships between race, ancestry, tumor molecular portraits and immunological biomarkers in TNBC patients from Louisiana, as well as the possible role of obesity in modifying tumor immunity. Specifically, we wish to: 1) Retrospectively determine whether the molecular portraits of TNBC and/or the expression of immunological biomarkers differ between EA and AA patients, and whether obesity is associated with unfavorable immunological biomarkers irrespective of race and 2) Prospectively characterize and compare genomic and immunological portraits and response to neoadjuvant treatment of stage II/II TNBC tumors from EA versus AA patients, obese versus non- obese, and pre- versus post-treatment samples in cases that do not achieve pCR. These data will provide the basis for the development of novel clinically actionable biomarkers applicable to AA patients with TNBC and common comorbidities such as obesity. Additionally, this data can be used to inform decisions regarding prevention strategies, and to optimize treatment for underserved patients. As novel treatments such as immunotherapy become part of the therapeutic arsenal, our data will form the basis for hypothesis-driven studies of clinically informative biomarkers in our patient population.

摘要 - 项目1 路易斯安那州三阴性乳腺癌（TNBC）的发生率是美国最高的之一， 特别是在非裔美国人（AA）妇女中。与 欧美（EA）。这些显然分开的条件可能与遗传学，表观遗传学和 慢性炎症。 TNBC是一种遗传异质性疾病，包括多个分子 基于转录本表达和体细胞突变的亚型。这些子类型对 标准化学疗法，但尚未在临床实践中常规，尚不清楚它们适用于AA 患者。我们的初步数据和文献表明分子特征和炎症细胞 TNBC浸润的T细胞可能会提供重要的预后信息。作为P20计划的一部分 赠款项目，我们将探讨种族，祖先，肿瘤分子肖像和 来自路易斯安那州TNBC患者的免疫生物标志物，以及肥胖症在修饰中的可能作用 肿瘤免疫。具体而言，我们希望：1）回顾性确定分子肖像是否是 EA和AA患者之间的TNBC和/或免疫生物标志物的表达不同， 肥胖是否与不利的免疫生物标志物相关，而不论种族如何，2） 前瞻性地表征和比较基因组和免疫肖像以及对 来自EA与AA患者的II/II期TNBC肿瘤的新辅助治疗 在无法实现PCR的情况下，肥胖和治疗后样品和后处理样本。这些数据将 为开发适用于AA患者的新型临床可行的生物标志物的开发提供了基础 TNBC和常见合并症，例如肥胖。此外，这些数据可用于为决策提供信息 关于预防策略，并优化服务不足的患者的治疗。作为新颖的治疗 随着免疫疗法成为治疗库的一部分，我们的数据将构成假设驱动的基础 对我们患者人群中临床信息丰富的生物标志物的研究。