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Aberrant immunity in the oral cavity—a link with rheumatoid arthritis? 口腔免疫异常--与类风湿性关节炎有关?
Pub Date : 2024-06-14 DOI: 10.3389/froh.2024.1430886
Jennifer Malcolm, Shauna Culshaw
There are well established epidemiological links between rheumatoid arthritis and periodontitis. Recent data have started to shed light on the mechanisms that might underlie the relationship between these two complex diseases. Unravelling the roles of distinct pathways involved in these mechanisms has the potential to yield novel preventative and therapeutic strategies for both diseases. Perhaps most intriguingly, this represents an area where understanding the biology in the oral cavity might reveal fundamental advances in understanding immune regulation and the relationships between the host and microbiome. Here we seek to discuss aspects of the adaptive immune response that might link periodontitis and rheumatoid arthritis.
类风湿性关节炎和牙周炎之间的流行病学联系已经得到证实。最近的数据已经开始揭示这两种复杂疾病之间的关系机制。揭示参与这些机制的不同途径的作用,有可能为这两种疾病提供新的预防和治疗策略。也许最令人感兴趣的是,在这一领域,对口腔生物学的了解可能会揭示在理解免疫调节以及宿主与微生物组之间关系方面的根本性进展。在此,我们试图讨论可能将牙周炎和类风湿性关节炎联系起来的适应性免疫反应的各个方面。
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引用次数: 0
Resin tags formation by modified Renewal MI formulations in a carious dentine model 在龋坏牙本质模型中使用改良 Renewal MI 配方形成树脂标记
Pub Date : 2024-06-14 DOI: 10.3389/froh.2024.1420541
Nabih Alkhouri, W. Xia, Paul Ashley, Anne Young
To determine which components in a new restorative material (Renewal MI) improve its ability to form resin tags within demineralized dentine.Varied components included polylysine (PLS), monocalcium phosphate (MCP), powder to liquid ratio (PLR), 4-methacryloyloxyethyl trimellitate anhydride (4META), and polypropylene glycol dimethacrylate (PPGDMA). Urethane dimethacrylate (UDMA), containing PPGDMA (24 wt%) and 4META (3 wt%), was mixed with glass filler with MCP (8 wt%) and PLS (5 wt%). PLR was 3:1 or 5:1. Reducing MCP and/or PLS to 4 and 2 wt% respectively or fully removing MCP, PLS, 4META or PPGDMA gave 16 formulations in total. Renewal MI, Z250 (with or without Scotchbond Universal adhesive) and Activa were used as commercial comparators. Collagen discs were obtained by totally demineralizing 2 mm thick, human, premolar, coronal dentine discs by immersion in formic acid (4M) for 48 h. The restorative materials were then applied on top (n = 3), before dissolving the collagen in sodium hypochlorite (15%). SEM/EDX was employed to determine resin tags length, composition, and surface coverage.Tags were >400, 20 and 200 µm and covered 62, 55 and 39% of the adhesion interface for Renewal MI, Scotchbond and Activa, respectively. With experimental formulations, they were 200 and >400 µm long with high vs. low PLR and composed primarily of polymerized monomers. Percentages of the adhesion interface covered varied between 35 and 84%. Reducing PLS or MCP caused a decline in coverage that was linear with their concentrations. Reducing MCP had lesser effect when PLS or PLR were low. Removal of 4META caused a greater reduction in coverage than PPGDMA removal.PLS, MCP, 4META, PPGDMA and low PLR together enhance Renewal MI tags formation in, and thereby sealing of, demineralized dentine.
目的:确定新型修复材料(Renewal MI)中的哪些成分可提高其在脱矿牙本质中形成树脂标记的能力。各种成分包括聚赖氨酸(PLS)、磷酸一钙(MCP)、粉液比(PLR)、4-甲基丙烯酰氧乙基偏苯三酸酐(4META)和聚丙二醇二甲基丙烯酸酯(PPGDMA)。含有 PPGDMA(24 wt%)和 4META (3 wt%)的聚氨酯二甲基丙烯酸酯(UDMA)与玻璃填料 MCP(8 wt%)和 PLS(5 wt%)混合。PLR 为 3:1 或 5:1。将 MCP 和/或 PLS 分别降至 4 和 2 wt%,或完全去除 MCP、PLS、4META 或 PPGDMA 后,共得到 16 种配方。Renewal MI、Z250(含或不含 Scotchbond 通用粘合剂)和 Activa 被用作商业对比。胶原盘是将 2 毫米厚的人类前臼齿冠牙本质盘在甲酸(4M)中浸泡 48 小时后完全脱矿而得到的。然后在上面涂上修复材料(n = 3),再用次氯酸钠(15%)溶解胶原蛋白。使用 SEM/EDX 确定树脂标签的长度、成分和表面覆盖率。Renewal MI、Scotchbond 和 Activa 的标签长度分别大于 400、20 和 200 µm,覆盖了 62、55 和 39% 的粘附界面。实验配方的标签长度分别为 200 微米和大于 400 微米,PLR 有高有低,主要由聚合单体组成。粘合界面的覆盖率在 35% 到 84% 之间。减少 PLS 或 MCP 会导致覆盖率下降,且与它们的浓度呈线性关系。当 PLS 或 PLR 较低时,减少 MCP 的影响较小。PLS、MCP、4META、PPGDMA 和低 PLR 可共同促进脱矿牙本质中 Renewal MI 标记的形成,从而达到封闭的目的。
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引用次数: 0
The Canadian dental care plan and the senior population 加拿大牙科保健计划和老年人口
Pub Date : 2024-06-12 DOI: 10.3389/froh.2024.1385482
Anil Menon, Robert J. Schroth, K. Hai-Santiago, Kathy Yerex, M. Bertone
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引用次数: 0
An inflammatory paradox: strategies inflammophilic oral pathobionts employ to exploit innate immunity via neutrophil manipulation 炎症悖论:嗜炎口腔致病菌通过操纵中性粒细胞利用先天免疫力的策略
Pub Date : 2024-06-11 DOI: 10.3389/froh.2024.1413842
Dustin L. Higashi, Hua Qin, Christina Borland, Jens Kreth, Justin Merritt
Inflammatory dysbiotic diseases present an intriguing biological paradox. Like most other infectious disease processes, the alarm bells of the host are potently activated by tissue-destructive pathobionts, triggering a cascade of physiological responses that ultimately mobilize immune cells like neutrophils to sites of active infection. Typically, these inflammatory host responses are critical to inhibit and/or eradicate infecting microbes. However, for many inflammatory dysbiotic diseases, inflammophilic pathobiont-enriched communities not only survive the inflammatory response, but they actually obtain a growth advantage when challenged with an inflammatory environment. This is especially true for those organisms that have evolved various strategies to resist and/or manipulate components of innate immunity. In contrast, members of the commensal microbiome typically experience a competitive growth disadvantage under inflammatory selective pressure, hindering their critical ability to restrict pathobiont proliferation. Here, we examine examples of bacteria-neutrophil interactions from both conventional pathogens and inflammophiles. We discuss some of the strategies utilized by them to illustrate how inflammophilic microbes can play a central role in the positive feedback cycle that exemplifies dysbiotic chronic inflammatory diseases.
炎症性菌群失调性疾病是一个耐人寻味的生物学悖论。与大多数其他感染性疾病过程一样,宿主的警钟被组织破坏性病原体有效激活,引发一连串生理反应,最终调动中性粒细胞等免疫细胞前往活动感染部位。通常,这些宿主炎症反应对于抑制和/或根除感染微生物至关重要。然而,对于许多炎症性菌群失调疾病来说,嗜炎病原菌富集的群落不仅能在炎症反应中存活下来,而且在面临炎症环境的挑战时实际上还能获得生长优势。对于那些已经进化出各种策略来抵御和/或操纵先天性免疫成分的生物来说,情况尤其如此。与此相反,共生微生物群的成员在炎症选择性压力下通常会经历竞争性生长劣势,从而阻碍它们限制病原菌增殖的关键能力。在这里,我们研究了传统病原体和嗜炎菌中细菌与中性粒细胞相互作用的例子。我们将讨论它们所采用的一些策略,以说明嗜炎微生物如何在正反馈循环中发挥核心作用,而正反馈循环正是慢性炎症性疾病的典型特征。
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引用次数: 0
Co-design of health educational materials with people experiencing homelessness and support workers: a scoping review 与无家可归者和辅助人员共同设计健康教育材料:范围界定审查
Pub Date : 2024-06-11 DOI: 10.3389/froh.2024.1355349
Andrea Rodriguez, Shambhunath Shambhunath, Thushani Indumani Devi Wijesiri, Camila Biazus-Dalcin, Niall Mc Goldrick
People experiencing homelessness are often marginalised and encounter structural barriers when seeking healthcare. Community-based oral health interventions highlighted the need of well-trained practitioners for the successful engagement of service users and behaviour change. However, a lack of adequate information and specific training has been previously reported. The adoption of inclusive approaches, such as co-design, to develop tailored and meaningful health promotion training and educational materials capable of addressing the specific needs of this group is required. Co-design entails active involvement of different groups in research processes that acknowledge participants' needs and expectations. This scoping review aims to identify the available literature on the participation of people experiencing homelessness and/or their support workers in co-designing health and oral health promotion training/educational materials, approaches adopted, and barriers and enablers to develop these materials.The Joanna Briggs Institute (JBI) Scoping Review Methodology informed the development of the scoping review. The protocol was registered on the Open Science Framework. Six electronic databases (Medline (OVID), PsychInfo (OVID), Scopus, Web of Science, Applied Social Sciences Index and Abstracts (ASSIA) (ProQuest) and CINHAL) were systematically searched using MeSH terms. An extensive grey literature search, consultation with experts and hand searching of reference lists took place. Records were screened independently and in duplicate using the Rayyan Qatar Computing Research Institute (QCRI) online tool, followed by qualitative content analysis involving descriptive data coding.Eight studies/materials were included. Key approaches adopted to co-design, enablers and barriers were captured. The enablers were inclusivity, a safe environment for positive participation, empowerment and flexibility, the barriers were difficulty in recruiting and sustaining participation, power differentials, and limited resources.The evidence in this area is limited. This scoping review provided foundations for further research to examine the impact of different components of the co-design process including the environment in which the co-design process is conducted. Further studies with experimental design and reported using appropriate study design frameworks detailing active components of the co-design process would strengthen the evidence base in this area.
无家可归者往往被边缘化,在寻求医疗保健时会遇到结构性障碍。以社区为基础的口腔健康干预措施强调,需要训练有素的从业人员,才能让服务用户成功参与并改变行为。然而,以前曾有过缺乏足够信息和专门培训的报道。因此,需要采用共同设计等包容性方法,开发量身定制的、有意义的健康促进培训和教育材料,以满足这一群体的特殊需求。共同设计要求不同群体积极参与研究过程,并承认参与者的需求和期望。本范围界定综述旨在确定有关无家可归者和/或其支持工作者参与共同设计健康和口腔健康促进培训/教育材料的现有文献、所采用的方法以及开发这些材料的障碍和推动因素。该协议已在开放科学框架上注册。使用 MeSH 术语对六个电子数据库(Medline (OVID)、PsychInfo (OVID)、Scopus、Web of Science、Applied Social Sciences Index and Abstracts (ASSIA) (ProQuest) 和 CINHAL)进行了系统检索。此外,还进行了广泛的灰色文献检索,咨询了专家,并对参考文献目录进行了人工检索。使用 Rayyan Qatar Computing Research Institute (QCRI) 在线工具对记录进行了一式两份的独立筛选,然后进行了描述性数据编码的定性内容分析。共纳入了八项研究/资料,其中包括共同设计所采用的主要方法、促进因素和障碍。促进因素包括包容性、有利于积极参与的安全环境、赋权和灵活性,而障碍则是难以招募和维持参与、权力差异和资源有限。此次范围界定研究为进一步研究共同设计流程不同组成部分(包括开展共同设计流程的环境)的影响奠定了基础。进一步开展实验设计研究,并使用适当的研究设计框架详细报告共同设计过程的积极组成部分,将加强该领域的证据基础。
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引用次数: 0
Diversity and compositional differences in the oral microbiome of oral squamous cell carcinoma patients and healthy controls: a scoping review 口腔鳞状细胞癌患者和健康对照组口腔微生物群的多样性和组成差异:范围综述
Pub Date : 2024-06-11 DOI: 10.3389/froh.2024.1366153
M. C. van Dijk, J. F. Petersen, J. E. Raber-Durlacher, J. B. Epstein, A. M. G. A. Laheij
The human oral microbiome may play a role in the development of oral squamous cell carcinoma. The aim of this scoping review was to examine microbial diversity and differences in the composition of the oral microbiome between OSCC patients and healthy controls.A literature search (in PubMed and Embase.com) was performed on January 9, 2023. The outcome variables used from the included studies of this review were alpha- and beta diversity and oral microbiome composition profiles for each taxonomic level (phylum-, class-, order-, genus- and species level).Thirteen out of 423 studies were included in this review compromising 1,677 subjects, of which 905 (54.0%) were OSCC patients and 772 (46.0%) were healthy controls. Most studies found a higher alpha diversity in the OSCC patient group and significantly different beta diversities between OSCC patient samples and healthy control samples. Studies reported more abundant Fusobacteria (on phylum level), Fusobacterium (on genus level), Fusobacterium nucleatum, Porphyromonas endodontalis and Prevotella intermedia (on species level) in OSCC patients. The healthy control group had more abundant Actinobacteria (on phylum level), Streptococcus and Veilonella (on genus level) and Veilonella parvula (on species level) according to most studies.Our findings show differences in oral microbiome diversity and composition in OSCC patients. Clinical implications demand continuing study. Development of internationally accepted standard procedures for oral sample collection and oral microbiota analysis is needed for more conclusive and clinically relevant comparisons in future research.
人类口腔微生物组可能在口腔鳞状细胞癌的发病过程中发挥作用。本范围综述旨在研究OSCC患者和健康对照组之间的微生物多样性和口腔微生物组组成的差异。2023年1月9日进行了文献检索(PubMed和Embase.com)。本综述所纳入研究的结果变量为α-和β-多样性以及各分类级别(门、纲、目、属和种级别)的口腔微生物组组成概况。大多数研究发现,OSCC 患者组的α多样性较高,而 OSCC 患者样本与健康对照组样本的β多样性有显著差异。研究报告显示,OSCC 患者体内的镰刀菌(门)、镰刀菌(属)、核镰刀菌、牙髓卟啉菌和中间普雷沃菌(种)含量更高。我们的研究结果表明,OSCC 患者口腔微生物组的多样性和组成存在差异。我们的研究结果表明,OSCC 患者口腔微生物组的多样性和组成存在差异。需要制定国际公认的口腔样本采集和口腔微生物群分析标准程序,以便在未来的研究中进行更具结论性和临床相关性的比较。
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引用次数: 0
Histological pattern of tumor inflammation and stromal density correlate with patient demographics and immuno-oncologic transcriptional profile in oral squamous cell carcinoma 肿瘤炎症的组织学模式和基质密度与口腔鳞状细胞癌患者的人口统计学特征和免疫肿瘤学转录特征有关
Pub Date : 2024-06-06 DOI: 10.3389/froh.2024.1408072
V. Theofilou, Ioana Ghita, Manar A. Elnaggar, Risa Chaisuparat, John C. Papadimitriou, Soren M. Bentzen, D. Dyalram, J. Lubek, Robert A. Ord, Rania H. Younis
Oral squamous cell carcinoma (OSCC) is the most prevalent oral malignancy, with emerging interest in the characterization of its tumor microenvironment. Herein, we present a comprehensive histological analysis of OSCC stromal density and inflammation and their relationship with patient demographics, clinicopathologic features and immuno-oncologic signatures.Eighty-seven completely excised OSCC tissues were prospectively collected and scored for histopathologic inflammatory subtypes [HIS]—inflamed (INF), immune-excluded (IE) and immune-desert (ID), peritumoral stromal inflammation (PTSI), and peritumoral stromal fibrosis (PTSF). Scoring of inflammation was complemented by Semaphorin 4D immunohistochemistry. NanoString differential gene expression (DGE) analysis was conducted for eight OSCC cases representative of the inflammatory and stromal subtypes and the demographic groups.PTSF correlated with male gender (p = 0.0043), smoking (p = 0.0455), alcohol consumption (p = 0.0044), increased tumor size (p = 0.0054), and advanced stage (p = 0.002). On the contrary, PTSI occurred predominantly in females (p = 0.0105), non-drinkers (p = 0.0329), and small tumors (p = 0.0044). Transcriptionally, decreased cytokine signaling, and oncogenic pathway activation were observed in HIS-IE. Smokers and males displayed decreased global immune-cell levels and myeloid-cell predominance.Our work describes OSCC stromal and inflammatory phenotypes in correlation with distinct patient groups and DGE, highlighting the translational potential of characterizing the tumor microenvironment for optimal patient stratification.
口腔鳞状细胞癌(OSCC)是发病率最高的口腔恶性肿瘤,人们对其肿瘤微环境特征的研究兴趣日渐浓厚。在此,我们对OSCC基质密度和炎症及其与患者人口统计学、临床病理学特征和免疫肿瘤学特征的关系进行了全面的组织学分析。我们前瞻性地收集了87例完全切除的OSCC组织,并对组织病理学炎症亚型[HIS]--炎症(INF)、免疫排斥(IE)和免疫惰性(ID)、瘤周基质炎症(PTSI)和瘤周基质纤维化(PTSF)进行了评分。通过 Semaphorin 4D 免疫组化对炎症进行评分。PTSF与男性性别(p = 0.0043)、吸烟(p = 0.0455)、饮酒(p = 0.0044)、肿瘤体积增大(p = 0.0054)和晚期(p = 0.002)相关。相反,PTSI 主要发生在女性(p = 0.0105)、不饮酒者(p = 0.0329)和小肿瘤(p = 0.0044)中。在转录方面,HIS-IE中观察到细胞因子信号转导减少和致癌通路激活。我们的研究描述了OSCC基质和炎症表型与不同患者群体和DGE的相关性,突出了表征肿瘤微环境以优化患者分层的转化潜力。
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引用次数: 0
Tendency of microbial adhesion to denture base resins: a systematic review 义齿基托树脂的微生物粘附倾向:系统性综述
Pub Date : 2024-05-16 DOI: 10.3389/froh.2024.1375186
Firas K. Alqarawi, Mohammed M Gad
Digital denture fabrication became an alternative method to conventional denture fabrication. However reviewing the antimicrobial performance of newly introduced digital fabrication methods in comparison to the conventional method is neglected. Aim of study: this review was to compare the antiadherence properties of various CAD-CAM subtractive (milled), additive (3D printed) conventional denture base resins. In order to answer the developed PICO question: “Does CAD-CAM milled and 3D printed denture base resins have microbiological antiadherence properties over the conventional ones?” We included comparative studies on digitally fabricated Denture base resins with conventionally fabricated one in term of microbial adhesion.All in vitro studies investigated the microbial adherence to CAD-CAM milled and 3D printed denture base resins in comparison to conventional were searched in the PubMed, Web of Sciences, and Scopus databases up to December 2023.Fifteen studies have been investigated the microbial adhesion to milled and 3D printed denture base resins. CAD-CAM milled resins significantly decreased the microbial adhesion when compared with the conventional resins and 3D printed resins, while the later showed a high tendency for microbial adhesion. The addition of antifungal agents to 3D printed resins significantly reduced C. albicans adhesion. In terms of 3D printing parameters, printing orientation affected adherence while printing technology had no effect on microbial adhesion.Denture base materials and fabrication methods significantly affect the microbial adhesion. CAD-CAM milled denture base resins demonstrated low microbial adhesion. 3D-printed resins showed high tendency for C. albicans adhesion. The antiadherent properties of 3D-printed resins can be improved by incorporating antifungal agents or changing the printing parameters, but further investigations are required to validate these modifications.
数码义齿制作已成为传统义齿制作的替代方法。然而,与传统方法相比,对新引入的数字化义齿制作方法的抗菌性能的审查却被忽视了。研究目的:本综述旨在比较各种 CAD-CAM 减法(铣削)、加法(3D 打印)传统义齿基底树脂的抗粘连性能。为了回答所提出的 PICO 问题:"CAD-CAM铣制和三维打印义齿基托树脂与传统义齿基托树脂相比,是否具有抗微生物粘附性?截至 2023 年 12 月,我们在 PubMed、Web of Sciences 和 Scopus 数据库中检索了所有调查了与传统义齿基托树脂相比,CAD-CAM 铣制和 3D 打印义齿基托树脂的微生物粘附性的体外研究。与传统树脂和三维打印树脂相比,CAD-CAM 铣制树脂明显降低了微生物粘附性,而三维打印树脂则显示出较高的微生物粘附倾向。在三维打印树脂中添加抗真菌剂可明显减少白僵菌的附着。在三维打印参数方面,打印方向影响粘附性,而打印技术对微生物粘附性没有影响。CAD-CAM 铣制的义齿基托树脂表现出较低的微生物粘附性。而三维打印树脂则显示出较高的白僵菌粘附倾向。通过加入抗真菌剂或改变打印参数,可以提高三维打印树脂的抗粘附性能,但还需要进一步的研究来验证这些改良措施。
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引用次数: 0
Embedding patient and public involvement into a doctoral study: developing a point-of-care HIV testing intervention for dental settings 将患者和公众参与纳入博士研究:为牙科机构制定护理点艾滋病毒检测干预措施
Pub Date : 2024-05-15 DOI: 10.3389/froh.2024.1359132
J. Doughty, J. Preston, M. Paisi, A. Hudson, F. Burns, S. R. Porter, R. G. Watt
Patient and Public Involvement (PPI) can have a positive impact on research. PPI can make research more meaningful and appropriate as well as preventing research waste. For decades, patient advocates with HIV have played a key part in public health and research. This article presents the PPI activity undertaken during a doctoral study. The aim of this article is to demonstrate how PPI was embedded into a doctoral study that explored the feasibility of HIV testing in dental settings.Patients and the public were invited to be involved with the feasibility study through various organisations and charities. A comprehensive PPI activity strategy was devised, and appropriate funding was obtained. Patients and the public were predominantly consulted or collaboratively involved with several aspects of the study.Patients and the public positively contributed to the intervention development and the resources supporting its implementation. As a result, the study resources (i.e., questionnaire and information leaflets) were easier to read, and the intervention was more appropriate to the needs of patients. Furthermore, the training and focus groups conducted with dental patients and people with HIV benefitted from input of people with lived experience.PPI can be embedded within doctoral studies provided there is sufficient funding, flexibility, and supervisory support. However, PPI activity may be impacted by limited resource and a priori research protocol and funding agreements.
患者和公众参与 (PPI) 可以对研究产生积极影响。患者和公众参与可以使研究更有意义、更恰当,并防止研究浪费。几十年来,艾滋病患者倡导者在公共卫生和研究中发挥了重要作用。本文介绍了在一项博士研究中开展的公众宣传活动。本文旨在展示如何将公众宣传活动纳入一项博士研究,该研究探讨了在牙科环境中进行艾滋病检测的可行性。该研究通过各种组织和慈善机构邀请患者和公众参与可行性研究,制定了全面的公众参与活动战略,并获得了适当的资金。患者和公众对干预措施的制定以及支持其实施的资源做出了积极贡献。因此,研究资源(即调查问卷和信息传单)更易于阅读,干预措施也更符合患者的需求。此外,对牙科患者和艾滋病感染者进行的培训和焦点小组活动也得益于有生活经验者的参与。然而,PPI 活动可能会受到有限资源、先验研究协议和资助协议的影响。
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引用次数: 0
Fibroblasts from HPV-negative oropharynx squamous cell carcinomas stimulate the release of osteopontin from cancer cells via the release of IL-6 人乳头瘤病毒阴性口咽鳞状细胞癌的成纤维细胞通过释放 IL-6 刺激癌细胞释放补骨脂素
Pub Date : 2024-05-13 DOI: 10.3389/froh.2024.1390081
Naeima Yahia Hendawi, Hannah L. Crane, Hisham Mehanna, R. Bolt, Daniel W. Lambert, Keith D. Hunter
HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) shows distinct biological and clinical behaviour when compared to HPV-negative OPSCC. The overall role of the tumour microenvironment (TME) in head and neck cancer progression and metastasis has been studied intensively, but differences in HPV-negative and HPV-positive OPSCCs are less understood.To investigate the role of cancer-associated fibroblasts (CAFs) and the functional interactions of normal tonsil fibroblasts (NTFs) and OP CAFs with HPV+ and HPV− OPSCC cells and explore novel candidates in tumour-fibroblast crosstalk.A retrospective cohort of 143 primary OPSCCs was characterised using HPV16/18 RNAScope assay, p16 IHC and ɑ-SMA. Four OPSCC, three NTF and 2 new OPSCC CAF cultures were used to assess the cytokine-based interactions using cytokine arrays on conditioned media (CM), followed by co-culture approaches to identify the role of individual cell types and the role of OPN (SPP1) and IL-6 in SCC/fibroblast communication.HPV status was associated with better overall survival. Although ɑ-SMA expression was observed in both OPSCC subtypes, it provided survival stratification only in the HPV−positive group (Log-Rank p = 0.02). Three normal tonsillar fibroblast cultures (NTFs) were characterised by induction of myofibroblastic and senescent phenotypes with similar reactivity to our published NOF phenotype. The OPSCC-derived CAF cultures were characterised and their baseline myofibroblastic and senescence phenotypes varied. Cytokine array analysis of CM to identify novel candidates in the crosstalk between OPSCC tumour cells and NTFs/CAFs identified differences in the cytokine profiles on comparison of HPV+ and HPV− OPSCC cells. Osteopontin (OPN/SPP1) was identified, particularly in HPV-negative OPSCC cell analyses. We have demonstrated that OPN was produced by the OPSCC cells and revealed an associated upregulation of IL-6 in fibroblasts. Treatment of NTFs with rOPN showed alteration in phenotype, including increased contraction and IL-6 production. Antibody-mediated inhibition of CD44v6 attenuated the production of IL-6 by OPN in NTFs.This investigation with OPSCC fibroblasts provides novel insights into the role of CAFs in OPSCC mediated by IL-6 stimulated release of OPN from HPV negative OPSCC cells. The details of HPV-positive SCC cell/fibroblast cytokine crosstalk remain elusive.
与HPV阴性口咽鳞状细胞癌(OPSCC)相比,HPV相关口咽鳞状细胞癌(OPSCC)显示出不同的生物学和临床表现。肿瘤微环境(TME)在头颈部癌症进展和转移中的整体作用已得到深入研究,但对HPV阴性和HPV阳性口咽鳞癌的差异了解较少。为了研究癌症相关成纤维细胞(CAFs)的作用以及正常扁桃体成纤维细胞(NTFs)和OP CAFs与HPV+和HPV- OPSCC细胞的功能相互作用,并探索肿瘤-成纤维细胞串扰的新候选者。在条件培养基(CM)上使用细胞因子阵列对4个OPSCC、3个NTF和2个新的OPSCC CAF培养物进行细胞因子相互作用评估,然后采用共培养方法确定单个细胞类型的作用以及OPN(SPP1)和IL-6在SCC/成纤维细胞沟通中的作用。虽然ɑ-SMA表达在两种OPSCC亚型中都能观察到,但只有在HPV阳性组中才能提供生存分层(Log-Rank p = 0.02)。三种正常扁桃体成纤维细胞培养物(NTFs)的特点是诱导肌成纤维细胞和衰老表型,其反应性与我们已发表的 NOF 表型相似。OPSCC 衍生 CAF 培养物的特征及其基线肌成纤维细胞和衰老表型各不相同。对CM进行细胞因子阵列分析,以确定OPSCC肿瘤细胞与NTFs/CAFs之间相互作用的新候选者,结果发现HPV+和HPV- OPSCC细胞的细胞因子谱存在差异。特别是在 HPV 阴性的 OPSCC 细胞分析中发现了骨化蛋白(OPN/SPP1)。我们证明 OPN 由 OPSCC 细胞产生,并揭示了成纤维细胞中 IL-6 的相关上调。用rOPN处理NTF后,表型发生了改变,包括收缩和IL-6生成增加。这项利用 OPSCC 成纤维细胞进行的研究为我们提供了新的视角,揭示了 CAFs 在 OPSCC 中的作用,即通过 IL-6 刺激 HPV 阴性 OPSCC 细胞释放 OPN。HPV阳性SCC细胞/成纤维细胞细胞因子串扰的细节仍然难以捉摸。
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Frontiers in Oral Health
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