Analysis of local microbiota in patients with oropharyngeal squamous cell carcinoma: Inter- and intra-individual differences and interaction with the immunological tumor microenvironment

与皮肤和肠道一样，口腔和咽部也充满了细菌和其他微生物。近年来，细菌微生物群的潜在功能作用在肿瘤学领域引起了极大的兴趣。特别是对于胃肠道肿瘤，已经证明局部（肠道）微生物组（定义为生活在人体内部或特定部位的微生物的集体基因组）的组成强烈影响肿瘤进展，对治疗的反应和抗肿瘤免疫。对与头颈癌相关的微生物群知之甚少。目前，肿瘤、微生物群和免疫系统之间的潜在相关性和相互作用仍然难以捉摸。在本研究项目中，我们计划对口咽癌患者的细菌微生物群进行分子表征，以探索与临床分子肿瘤特性，临床结果和免疫肿瘤微环境的潜在联系。为此，我们将通过已建立的16 S-RNA测序来识别微生物群。将监测临床参数和结局。将通过多参数免疫荧光结合最先进的数字图像分析技术获得肿瘤内免疫状态的全面表征。基于这些组织分析，我们最终将进行体外研究，以研究先前暴露于细菌刺激的肿瘤细胞和基质细胞对免疫细胞的募集。我们的方法基于以下假设：a）肿瘤相关微生物群和免疫细胞参与功能性串扰，以及B）这种串扰影响肿瘤免疫相互作用和肿瘤进展。我们的系统方法将使我们能够在未来的后续项目中识别和探索潜在的治疗干预措施，以靶向微生物群，肿瘤细胞和免疫细胞的相互作用。

Like the skin and the gut, the oral cavity and the pharynx are intensely populated by bacteria and other microorganisms. In recent years, the potential functional role of the bacterial microbiota has gained substantial interest in the field of oncology. Especially for tumors of the gastrointestinal tract, it has been demonstrated that the composition of the local (gut) microbiome (defined as the collective genomes of the microbes that live inside or on a specific site of the human body) strongly influences tumor progression, response to therapy and anti-tumor immunity. Much less is known about the microbiota associated with head and neck cancer. Potential correlations and interactions between tumor, microbiota and the immune system remain elusive at present. In this research project, we plan to perform a molecular characterization of the bacterial microbiota of patients with oropharyngeal carcinomas in order to explore potential connections with clinical-molecular tumor properties, clinical outcome, and the immunological tumor microenvironment. To this end, we will identify the microbiota by established 16S-RNA-Sequencing. Clinical parameters and outcome will be monitored. A comprehensive characterization of the intratumoral immune status will be obtained by multi-parameter immunofluorescence in combination with state-of-the art digital image analyses technologies. Based on these tissue analyses, we will finally conduct in vitro studies to investigate the recruitment of immune cells by tumor cells and stromal cells that were previously exposed to bacterial stimulation. Our approach is based on the following hypotheses: a) tumor-associated microbiota and immune cells engage in a functional cross-talk and b) this cross-talk affects tumor-immune-interaction and tumor progression. Our systematic approach will enable us to identify and explore potentially therapeutic interventions to target the interaction of microbiota, tumor cells and immune cells in a future follow-up project.