Project 2

项目2

• 批准号: 10265455
• 负责人: Jiyoung Ahn
• 金额: $ 16.92万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-17 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10265455
• 关键词: Accounting; Affect; Amino Acids; Animal Experiments; Bacteria; Biological; Biological Assay; Biological Factors; Colon Carcinoma; Colonic Neoplasms; Colorectal Cancer; Country; DNA; Data; Detection; Development; Diagnosis; Epithelial Cells; Ethnic group; Flow Cytometry; Fusobacterium; Goals; Health Services Accessibility; Human Microbiome; Immune response; Immune system; Immunophenotyping; Intervention; Knowledge; Lead; Leukocytes; Ligands; Malignant Neoplasms; Mediating; Mutation; Myeloid Cells; Outcome; Patients; Peptides; Play; Population; Prevention; Prevention approach; Race; Recurrence; Research; Role; Shapes; Shotgun Sequencing; Somatic Mutation; Stage at Diagnosis; Structure; T-Lymphocyte; Testing; Therapeutic; Tumor Tissue; antigen-specific T cells; cancer health disparity; cancer recurrence; colon cancer patients; colon tumorigenesis; comparative; cytokine; exhaustion; exome sequencing; experience; gut bacteria; gut microbiome; gut microbiota; health equity; high risk; immune function; immunogenic; improved; metagenome; microbial; microbiome; microbiome research; microbiome sequencing; mortality; neoantigens; neoplastic cell; novel; personalized approach; racial disparity; response; socioeconomics; tumor; tumor microenvironment; tumor-immune system interactions; whole genome

PROJECT SUMMARY U.S. Blacks have the highest mortality rate of colorectal cancer of any ethnic group in the country. To achieve colon cancer health equity, it is critical to determine the underlying biological factors associated with poorer colon cancer outcomes in Blacks, which could lead to tailored prevention and intervention approaches. The gut microbiota may play an important biologic role in racial disparities for colon cancer outcomes. Increasing evidence indicates that the gut microbiota influences innate and adaptive immune function in the tumor microenvironment. The tumor immune microenvironment is critical for the detection and destruction of nascent tumor cells. Our preliminary data suggest that healthy Blacks have a significantly different gut microbiome compared to Whites; importantly, we showed that these gut bacteria are further altered in colon cancer patients, supporting our hypothesis. Our animal experiments further suggest that gut bacteria modulate tumor immune microenvironment and affect the efficiency of cancer response to therapy. However, no studies have examined the relationship between the broader human microbiome, tumor immune microenvironment, and outcomes of colon cancer in the comparative research setting with Blacks and Whites. Our overarching goal is to achieve colon cancer health equity, by elucidating gut microbial factors associated with poorer colon cancer outcomes in Blacks. Our specific aims are 1) to identify gut bacteria associated with racial disparity in colon cancer and its recurrence, using full genome shotgun sequencing microbiome assay in 200 Black and 200 White colon cancer patients (Stage I-III); 2) to determine how the immune system mediates the microbiome’s effect on colon cancer disparity, using immunophenotyping assay, from 30-parameter flow cytometry, and neoantigen load, from whole exome sequencing, in tumors of 50 Black and 50 White colon cancer patients. This first microbiome study of colon cancer disparities will comprehensively investigate the gut microbiome and its role in shaping the tumor immune microenvironment. This project will help to achieve colon cancer health equity by generating novel information about the role of the microbiome in colon tumorigenesis and progression. Knowledge gained from this study may improve our ability to identify people at high risk of recurrence, particularly in Blacks. The new information may further lead to the development of tailored approaches to prevention and therapeutics that exploit microbially-driven immune responses in colon cancer.

项目摘要 美国黑人的结直肠癌死亡率是全国所有种族中最高的。实现 结肠癌的健康公平性，关键是要确定潜在的生物学因素与较差的结肠 黑人的癌症结果，这可能导致量身定制的预防和干预方法。 肠道微生物群可能在结肠癌结局的种族差异中发挥重要的生物学作用。增加 有证据表明，肠道微生物群影响肿瘤中的先天性和适应性免疫功能， 微环境肿瘤免疫微环境对于检测和破坏新生的肿瘤细胞是至关重要的。 肿瘤细胞我们的初步数据表明，健康的黑人有一个显着不同的肠道微生物组 重要的是，我们发现这些肠道细菌在结肠癌患者中进一步改变， 支持我们的假设我们的动物实验进一步表明，肠道细菌调节肿瘤免疫 微环境的影响，并影响癌症对治疗的反应效率。然而，没有研究检查 更广泛的人类微生物组，肿瘤免疫微环境和 结肠癌在比较研究设置与黑人和白人。 我们的首要目标是通过阐明相关的肠道微生物因素来实现结肠癌健康公平 黑人的结肠癌预后较差。我们的具体目标是：1）识别与 结肠癌及其复发的种族差异，使用全基因组鸟枪测序微生物组测定， 200名黑人和200名白色结肠癌患者（I-III期）; 2）确定免疫系统如何介导 微生物组对结肠癌差异的影响，使用免疫表型分析，来自30个参数流 50例黑人和50例白色结肠癌肿瘤中的细胞计数和来自全外显子组测序的新抗原负载 患者这是第一项关于结肠癌差异的微生物组研究，将全面调查肠道 微生物组及其在塑造肿瘤免疫微环境中的作用。 该项目将通过产生关于结肠癌患者的作用的新信息， 微生物组在结肠肿瘤发生和发展中的作用。从这项研究中获得的知识可以提高我们的能力 以确定复发风险高的人，特别是黑人。新的信息可能会进一步导致 开发定制的预防和治疗方法，利用微生物驱动的免疫 对结肠癌的反应