Microbial communities in mouse HPV+ oropharyngeal tumors
Cancers induced by high-risk human papillomavirus (HPV) such as oropharyngeal cancers are highly prevalent in Hispanics and when metastasis occurs the disease is most likely incurable. The immune checkpoint blockade targeting the receptor programmed death-1 (PD-1) is FDA approved for head and neck squamous cell carcinomas. Although it has shown significant clinical efficacy, more than 50% of these HNSCC patients do not respond to this therapy. Increasing evidence shows a crosstalk between immune, microbial and tumor cells that may modulate tumor development and treatment response. Also, gut microbial diversity has been implicated in responsiveness to immune checkpoint blockade treatment, in part due to promoting an anti-tumor immune response. However, there is a gap in knowledge, in regards, to the interplay between microbial communities present in the oral cavity and immune responses occurring in HPV+ oropharyngeal cancers, which may affect treatment responses. We have utilized a preclinical mouse model for HPV+ oropharyngeal cancer named mEER, that have been transduced with HPV-16 E6 and E7 and H-Ras, to study biological factors promoting resistance to immune checkpoint blockade. In this model, C57BL/6 mice (immunocompetent) implanted with mEER cells in the tongue partially respond to anti-PD-1 where around 50% of the treated mice clear the tumors. In contrast, mice implanted with mEER tumors subcutaneously in the flank do not respond to immune checkpoint blockade and tumors continue to grow. Therefore, we collected tongue and subcutaneous tumors from untreated mice to identify the microbial differences present at these locations as well as non-tumor tissue to identify microbial changes due to tumor development.