Immunological changes associated with antibiotic use in oropharyngeal cancer

Project summary/Abstract 30 lines Antibiotics are widely used to prevent infections, however, their use has been associated with reduced overall survival of oropharyngeal cancer patients. The underlying mechanisms by which this occurs is in part because of the effect antibiotics have on the gut microbiota which shape immune responses against tumors. Although most research has focused on the effect of antibiotics on the gut microbiota, limited studies have identified the impact of antibiotics on the oral microbiota and immune responses during oropharyngeal cancer development. We hypothesize that antibiotic use leads to a decrease in microbial diversity which impairs anti-tumor immune responses and therefore promotes oropharyngeal cancer development. For this, we will utilize preclinical models to compare the effect of oral and topical tetracycline application (common antibiotic used as preoperative prophylaxis in oropharyngeal cancer patients) on cancer treatment responses (Aim 1) and intratumoral microbial and immune changes (Aim 2). Since high-risk human papillomavirus cause oropharyngeal cancer, we will also recruit women infected with HPV to collect saliva for immune cell phenotyping and cytokine and microbiota profiling (Aim 3). We will compare immune and microbial profiles between patients who were taking or not antibiotics. Banked saliva samples will also be used. Results from this study could potentially change clinical practices by providing evidence of the impact antibiotics have on immune responses in the oral cavity which may impair oral health, cancer risk, and prognosis of oropharyngeal cancer patients. We will also be able to identify bacteria eliminated by antibiotics to develop therapeutics to recover the loss of beneficial bacteria in Hispanic women.