ABSTRACT: Viruses are the second leading cause of cancer worldwide, and human papillomavirus (HPV)-associated head and neck cancers are increasing in incidence in the United States. HPV preferentially infects the crypts of the tonsils rather than the surface epithelium. The present study sought to characterize the unique microenvironment within the crypts to better understand the host tropism of HPV to a lymphoid rich organ. Laser-capture microdissection of distinct anatomic areas (crypts, surface epithelium, and germinal centers) of the tonsil coupled with transcriptional analysis and multi-parameter immunofluorescence staining was performed and demonstrated that the tonsillar crypts are enriched with myeloid populations which co-express multiple canonical and non-canonical immune checkpoints, including PD-L1, CTLA-4, HAVCR2 (TIM-3), ADORA2A, IDO1, BTLA, LGALS3, CDH1, CEACAM1, PVR, and C10orf54 (VISTA). The resident monocytes may foster a permissive microenvironment that facilitates HPV infection and persistence. Furthermore, the myeloid populations within HPV-associated tonsil cancers co-express the same immune checkpoints, providing insight into potential novel immunotherapeutic targets for HPV-associated head and neck cancers. The associated paper "Myeloid cells are enriched in tonsillar crypts providing insight into the host tropism of HPV", Austin K. Mattox, Jessica Roelands, Talia Saal, Yang Cheng, Darawan Rinchai, Wouter Hendrickx, Geoffrey D. Young, Thomas J. Diefenbach, Alan E. Berger, William H. Westra, Justin A. Bishop, William C. Faquin, Francesco M. Marincola, Mikael J. Pittet, Davide Bedognetti, and Sara I. Pai; The American Journal of Pathology, Online ahead of print DOI:https://doi.org/10.1016/j.ajpath.2021.06.012
