Abstract 2252: Microbial profiling of the head and neck tumor microenvironment as a biomarker of clinical response to chemoradiation

Abstract

Abstract PURPOSE: Despite advances in cancer treatment, patients with advanced head and neck cancer (HNC) have a median overall survival of <1 year and 30% cure rate. Evidence suggests that microbiota may modulate the response to therapy through a crosstalk with cancer cells, immune cells, and inflammatory mediators. This study was conducted to profile the tumor microbiome of HNC patients to determine whether bacteria and fungi in the tumor microenvironment are associated with the clinical response to chemoradiation. METHODS: Fresh frozen tumor tissues from 30 newly diagnosed, treatment-naïve patients who received chemoradiation at Moffitt Cancer Center for squamous cell HNC were evaluated. Genomic DNA was extracted from 25mg of tissue. The V1-V3 hypervariable region of the bacterial 16S rRNA gene and fungal internal transcribed spacer (ITS) 1 region were sequenced using a PCR amplicon-mediated workflow on the Illumina MiSeq. 16S sequences were clustered into operational taxonomic units and taxonomic identification was determined using the RDP database and ITS sequences were classified using an in house reference database. Patients' charts were reviewed to ascertain clinical response 3, 6 and 12 months after treatment cessation. Response was dichotomized as complete (no evidence of disease) and incomplete (partial response, stable disease, and progressive disease). RESULTS: At the time of tumor collection, patients ranged in age from 20-79 years, and were predominantly men (83%) and current smokers (40%). The most common anatomic site was the oral cavity (70%) followed by the larynx (20%) and oropharynx (10%), and most were diagnosed at stage 4 (87%). Three, 6 and 12 months after treatment cessation, 4 (14%), 9 (36%), and 10 (40%) patients had an incomplete response to therapy, respectively. Bacterial sequencing was successful in 29 (97%) samples and fungal in 15 (50%). Clustering analyses of bacterial abundance profiles suggested that 4 types of communities existed, each dominated by Fusobacterium, Prevotella, Streptococcus, or Treponema. HNC patients with incomplete clinical responses (3, 6, or 12 months after treatment) were more likely to have treatment-naïve tumors dominated by Fusobacterium (cluster 1; 56%) than any other genus, whereas patients with complete clinical responses were more likely to have treatment-naïve tumors dominated by Prevotella (cluster 2; 40%) than any other genus. None of the patients with incomplete responses were dominated by Streptococcus (cluster 3) or Treponema (cluster 4). Fungal ITS profiling revealed that the tumor microbiome was largely dominated by the fungi Malassezia. CONCLUSIONS: The current study demonstrates that intratumoral bacterial profiles dominated by Prevotella may serve as a biomarker of improved prognosis, while profiles dominated by Fusobacterium may indicate a poor prognosis following chemoradiation in HNC patients. Citation Format: Christine M. Pierce Campbell, Bo-Young Hong, Maria F. Gomez, Blake M. Hanson, Erica Sodergren, Sybil T. Sha, Jeffery S. Russell, George M. Weinstock. Microbial profiling of the head and neck tumor microenvironment as a biomarker of clinical response to chemoradiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2252. doi:10.1158/1538-7445.AM2017-2252