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

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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.