Immune and Microbial Signatures Associated with PD-1 Blockade Sensitivity in a Preclinical Model for HPV+ Oropharyngeal Cancer.

Simple Summary: The United States is suffering from an epidemic associated with infections with the Human Papilloma Virus (HPV) that are responsible for the development of head and neck squamous cell carcinoma (HNSCC). Our study aims to characterize immune profiles, and the oral microbiota in oropharyngeal tumors associated with anti-PD-1 treatment response in a preclinical murine model for HPV+ oropharyngeal cancer. We confirmed 16 immune markers and specific bacteria in the oral cavity that differentiate between treatment responders and non-responders, which may be used as potential biomarkers for PD-1 blockade response. The United States is suffering from an epidemic associated with high-risk strains of the Human Papillomavirus (HPV) predominantly responsible for the development of head and neck squamous cell carcinoma (HNSCC). Treatment with immune checkpoint inhibitors targeting programmed death 1 (PD-1) or its ligand PD-L1 has shown poor efficacy in HNSCC patients, observing only a 20–30% response. Therefore, biological marker identification associated with PD-1 blockade response is important to improve prognosis and define novel therapeutics for HNSCC patients. Therapy response was associated with increased frequencies of activated CD27+T cells, activated CD79a+ B cells, antigen-presenting CD74+ dendritic and B cells, and PD-L1+ and PD-L2+ myeloid-derived suppressor cells (MDSCs). The oral microbiota composition differed significantly in mice bearing tongue tumors and treated with anti-PD-1. A higher abundance of Allobaculum, Blautia, Faecalibacterium, Dorea, or Roseburia was associated with response to the therapy. However, an increase in Enterococcus was attributed to tongue tumor-bearing non-responding mice. Our findings indicate that differences in immune phenotypes, protein expression, and bacterial abundance occur as mice develop tongue tumors and are treated with anti-PD-1. These results may have a clinical impact as specific bacteria and immune phenotype could serve as biomarkers for treatment response in HNSCC. [ABSTRACT FROM AUTHOR]