ILANIT 2023

Characterizing the head and neck intra-tumoral microbiome

Nadeem Darawshe 1 Margo Musleh 1,2 Elias Saba 1 Maria Farhat 1 Hiromichi Kawasaki 2 Nardy Casap 2 Shay Sharon 1,2 Gabriel Nussbaum 1
1Hebrew University of Jerusalem, The Institute of Biomedical and Oral Research, Israel
2Hadassah Medical Center, Faculty of Dental Medicine, Hebrew University of Jerusalem, Department of Oral and Maxillofacial Surgery, Israel

Background: Oral squamous cell carcinoma (OSCC) develops in a complex environment containing a wide range of inflammatory factors and microbes. Furthermore, oral microbial dysbiosis in periodontal disease is associated with increased risk of OSCC, and bacteria associated with periodontal disease were shown to promote OSCC development in a preclinical model. Therefore, understanding what bacteria are present in human OSCC, and how they contribute to cancer progression, can lead to advances for prognosis and treatment.

Objectives: Identification of intracellular bacteria in OSCC by genetic and culture methods. Future studies will examine the link between tumor-associated bacteria and characteristics of the OSCC tumor or its microenvironment. Anti-microbial agents directed at tumor-associated bacteria will be tested to improve clinical outcomes.

Methods: (1) To isolate and identify cultivatable aerobic and anaerobic tumor-associated bacteria from freshly resected OSCC tumors. (2) To analyze the OSCC tumor microbiota using bacterial taxa-specific 16s rRNA fluorescent in-situ hybridization (FISH) on Paraffin-embedded OSCC samples. (3) To determine the OSCC tumor microbiome by 16s rRNA next-generation sequencing.

Results: Analysis of OSCC specimens revealed the presence of intracellular bacteria and distinct expression patterns, which varied between patients and between different regions of the tumor. Bacteria were successfully cultured from OSCC tumors, and intracellular bacteria were identified.

Conclusion: Microbiome characterization in cancer is an emerging field due to the discovery that many cancers harbor bacteria. Identifying the microbes associated with OSCC and understanding their functional role in tumor progression and response to therapy, will provide novel therapeutic targets to improve clinical outcomes.