Project 2

项目2

基本信息

批准号：
10044536
负责人：
Jiyoung Ahn
金额：
$ 17.66万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
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/10044536
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 Knowledge Lead Leukocytes Ligands Malignant Neoplasms Mediating Mutation Myeloid Cells Outcome Patients Peptides Play Population Prevention approach Preventive Intervention 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

项目摘要

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.

项目概要美国黑人的结直肠癌死亡率是该国所有族裔中最高的。结肠癌健康公平性，确定与较差结肠相关的潜在生物因素至关重要黑人的癌症结果，这可能会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果的种族差异中发挥重要的生物学作用。有证据表明肠道微生物群影响肿瘤的先天性和适应性免疫功能肿瘤免疫微环境对于新生肿瘤的检测和破坏至关重要。我们的初步数据表明，健康的黑人具有显着不同的肠道微生物组。与白人相比，我们发现这些肠道细菌在结肠癌患者中更明显，我们的动物实验进一步证明肠道细菌调节肿瘤免疫。然而，还没有研究证实微环境会影响癌症对治疗的反应效率。更广泛的人类微生物组、肿瘤免疫微环境和结果之间的关系结肠癌与黑人和白人的比较研究环境。我们的首要目标是通过阐明与结肠癌相关的肠道微生物因素来实现结肠癌健康公平黑人结肠癌预后较差，我们的具体目标是 1) 识别与结肠癌相关的肠道细菌。使用全基因组鸟枪法测序微生物组测定来研究结肠癌及其复发的种族差异 200 名黑人和 200 名白人结肠癌患者（I-III 期），以确定免疫系统如何介导使用免疫表型分析，通过 30 参数流分析微生物组对结肠癌差异的影响对 50 个黑人和 50 个白人结肠癌的肿瘤进行全外显子组测序的细胞计数和新抗原负载这项针对结肠癌差异的首次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。该项目将通过生成有关结肠癌作用的新信息来帮助股权实现结肠癌健康从这项研究中获得的知识可以提高我们的能力。识别复发风险高的人，特别是黑人，新信息可能会进一步导致这种情况。开发利用微生物驱动免疫的定制预防和治疗方法结肠癌的反应。