Project 1

项目1

• 批准号: 10044535
• 负责人: Richard Bernard Hayes
• 金额: $ 16.82万
• 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/10044535
• 关键词: Bacteria; Bioinformatics; Biological; Biological Factors; Cancer Burden; Carcinogen Metabolism; Cells; Corynebacterium; DNA Damage; DNA sequencing; Data; Development; Epithelial Cells; Etiology; Exhibits; Goals; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Human papillomavirus 16; Immune; Immune response; Incidence; Individual; Innate Immune System; Kingella; Knowledge; Lead; Metabolic; Metagenomics; Minority; Minority Groups; Mutation; Nested Case-Control Study; Oral; Oral Characters; Pathogenesis; Pattern recognition receptor; Population; Population Group; Population Heterogeneity; Prevention; Preventive Intervention; Race; Reporting; Research; Risk; Role; Shapes; Shotguns; Socioeconomic Factors; Socioeconomic Status; Somatic Mutation; Squamous Cell; Stimulus; Testing; The Cancer Genome Atlas; Therapeutic; Tumor-infiltrating immune cells; Work; Xenobiotics; bacteriome; base; cancer health disparity; carcinogenesis; cohort; fungus; health equity; high risk; immunogenic; improved; individualized prevention; innovation; insight; low socioeconomic status; microbial; microbiota; mortality; multilevel analysis; mycobiome; novel; oral bacteria; oral microbial community; oral microbiome; prospective; racial disparity; recruit; response; socioeconomic disparity; socioeconomics; transcriptome sequencing; tumor; tumor microbiota; tumor microenvironment; tumor-immune system interactions; underserved minority

PROJECT SUMMARY Squamous cell head and neck cancer (SCHNC) results in extensive physical disfigurement, and leads to ~40% 5-year mortality; thus its prevention is extremely important. Blacks and people with low socioeconomic status (SES) have a high burden of SCHNC. We hypothesize that the oral microbiota contribute to the racial and socioeconomic disparities in SCHNC. Oral bacteria and fungi can cause epithelial cell DNA damage by carcinogen metabolism, and some of these somatic mutations may be critical for SCHNC carcinogenesis. Bacteria and fungi may also promote carcinogenesis through immunogenic stimulus for innate immune system response via pattern recognition receptors, leading to immune cell recruitment and an altered tumor immune microenvironment. Thus, a microbial role in SCHNC development and the shaping of the tumor mutational and immune microenvironment is of great potential importance in the pathogenesis of SCHNC. Our preliminary data show that Blacks and individuals with low socioeconomic status exhibit lower overall oral microbiome diversity, particularly characterized by lower abundance of bacteria Corynebacterium and Kingella; we had previously reported that low abundance of these two bacteria is also associated with increased risk of SCHNC development. Our work further points to involvement of oral bacteria in carcinogen metabolism, with potential impact on tumor mutational load and immune infiltration. While this preliminary data supports our hypothesis, no studies have examined the comprehensive relationship between the oral microbiome, tumor microenvironment, and SCHNC in racial and socioeconomic minority populations. Our overall goal is to generate important biologic insights about oral microbial factors that underlie racial and socioeconomic disparities in SCHNC development. In this research, we expect to identify specific oral microbiota contributing to these disparities and to identify the tumor microbiota that influences host tumor mutation burden and the tumor immune microenvironment. This project will help to achieve SCHNC health equity by generating novel information from diverse population groups about the role of the oral microbiome in SCHNC development and pathogenesis. Knowledge gained may improve our ability to identify people at high risk of SCHNC, particularly in underserved minority groups. The new information may further lead to novel prevention and therapeutics approaches that exploit microbially-driven immune responses in SCHNC.

项目摘要 鳞状细胞头和颈癌（SCHNC）导致广泛的身体毁容，并导致约40％ 5年死亡率；因此，它的预防非常重要。黑人和社会经济地位低下的人 （SES）负担很高的Schnc负担。我们假设口腔菌群有助于种族和 Schnc的社会经济差异。口服细菌和真菌会引起致癌物上皮细胞DNA损伤 代谢，其中一些体细胞突变可能对SCHNC癌变至关重要。细菌和真菌 还可以通过免疫原性刺激通过模式促进癌变 识别受体，导致免疫细胞募集和肿瘤免疫微环境改变。因此， 微生物在SCHNC发育中的作用以及肿瘤突变和免疫微环境的塑造 在SCHNC的发病机理中具有巨大的重要性。我们的初步数据表明，黑人和 社会经济状况低的个体表现出较低的整体口服微生物组多样性，特别是特征 通过较低的细菌Corynebacterium和Kingella的丰度；我们以前曾报道过低丰度 这两种细菌也与SCHNC发育的风险增加有关。我们的工作进一步指向 口服细菌参与致癌代谢，对肿瘤突变负荷和 免疫浸润。尽管该初步数据支持我们的假设，但尚无研究检查 口腔微生物组，肿瘤微环境和Schnc之间的全面关系 社会经济少数民族。 我们的总体目标是生成有关种族和种族和种族微生物因素的重要生物学见解 SCHNC发展中的社会经济差异。在这项研究中，我们希望确定特定的口服微生物群 导致这些差异并确定影响宿主肿瘤突变负担的肿瘤微生物群 和肿瘤免疫微环境。该项目将通过产生生成 来自不同人口群体的新信息，介绍口腔微生物组在SCHNC发展中的作用 发病。获得的知识可能会提高我们识别出SCHNC高风险的人的能力，尤其是在 服务不足的少数群体。新信息可能会进一步导致新颖的预防和治疗方法 这种利用SCHNC中微生物驱动的免疫反应。