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 路易斯安那州的三阴性乳腺癌（TNBC）发病率是全国最高的， 尤其是非洲裔美国人（AA）。AA女性也处于肥胖的高风险中， 欧美人（EA）。这些明显不同的条件可能与遗传学、表观遗传学和 慢性炎症TNBC是一组遗传异质性疾病，包括多种分子生物学特征。 基于转录表达和体细胞突变的亚型。这些亚型对以下疾病的反应不同： 标准化疗，但尚未在临床实践中常规使用，并且尚不清楚它们在AA中的应用情况 患者我们的初步数据和文献表明，分子特征以及炎症细胞 浸润TNBC的T细胞可提供重要的预后信息。作为P20计划的一部分， 我们将探索种族、血统、肿瘤分子画像和 路易斯安那州TNBC患者的免疫学生物标志物，以及肥胖在改变 肿瘤免疫具体地说，我们希望：1）追溯确定是否分子肖像的 EA和AA患者之间的TNBC和/或免疫生物标志物的表达不同，并且 肥胖是否与不利的免疫学生物标志物相关，与种族无关，以及2） Proximity表征和比较基因组和免疫学特征以及对 来自EA与AA患者、肥胖与非肥胖患者的II/II期TNBC肿瘤的新辅助治疗 肥胖，以及在未达到pCR的情况下的治疗前与治疗后样本。这些数据将 为开发适用于AA患者的新型临床可操作生物标志物提供基础， TNBC和常见的合并症，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，并优化对服务不足的患者的治疗。作为新的治疗方法， 随着免疫疗法成为治疗武器库的一部分，我们的数据将成为假设驱动的基础。 在我们的患者人群中进行临床信息生物标志物的研究。