Project 1

项目摘要 鳞状细胞头颈癌（SCHNC）导致广泛的身体缺陷，并导致约40%的 5-年死亡率;因此，它的预防是非常重要的。黑人和社会经济地位低下的人 (SES)有很高的SCHNC负担。我们假设，口腔微生物群有助于种族和 社会经济不平等在SCHNC。口腔细菌和真菌可通过致癌物引起上皮细胞DNA损伤 这些体细胞突变中的一些可能是SCHNC致癌的关键。细菌和真菌 也可通过免疫原性刺激先天免疫系统应答促进致癌作用， 这可能与肿瘤细胞识别受体有关，从而导致免疫细胞募集和改变的肿瘤免疫微环境。因此，在本发明中， 微生物在SCHNC发展以及肿瘤突变和免疫微环境形成中的作用 在SCHNC的发病机制中具有重要的潜在意义。我们的初步数据显示， 社会经济地位低的个体表现出较低的整体口腔微生物组多样性，特别是 由于棒状杆菌和金氏杆菌的丰度较低，我们以前曾报道过， 这两种细菌也与SCHNC发展的风险增加有关。我们的工作进一步指出， 口腔细菌参与致癌物代谢，对肿瘤突变负荷有潜在影响， 免疫浸润虽然这些初步数据支持我们的假设，但还没有研究对 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。 我们的总体目标是产生关于口腔微生物因素的重要生物学见解，这些因素是种族和 在SCHNC发展中的社会经济差距。在这项研究中，我们希望确定特定的口腔微生物群， 并确定影响宿主肿瘤突变负荷的肿瘤微生物群 和肿瘤免疫微环境。该项目将通过产生 来自不同人群的关于口腔微生物组在SCHNC发展中的作用的新信息， 发病机制获得的知识可能会提高我们识别SCHNC高风险人群的能力，特别是在 弱势群体。新的信息可能会进一步导致新的预防和治疗方法 利用SCHNC中微生物驱动的免疫反应。

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.