biostudies-literatureMattox AKNIDCR NIH HHSNational Cancer InstituteNCI NIH HHSNational Institute of Dental and Craniofacial ResearchNational Institutes of HealthNIGMS NIH HHS1774-1786https://www.ebi.ac.uk/biostudies/studies/S-EPMC8491092biostudies-literatureUnknown191(10)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 viral 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 multiparameter immunofluorescence staining demonstrated that the tonsillar crypts are enriched with myeloid populations that co-express multiple canonical and noncanonical immune checkpoints, including PD-L1, CTLA-4The American journal of pathologyMyeloid Cells Are Enriched in Tonsillar Crypts, Providing Insight into the Viral Tropism of Human Papillomavirus.PMC8491092R01 CA2576231R01 DE025340P01 CA240239T32 GM136577R01 DE025340Faquin WCBedognetti DRinchai DYoung GDRoelands JMarincola FMCheng YBishop JAMattox AKPittet MJSaal TMPai SIDiefenbach TJBerger AEWestra WHHendrickx WfalseMyeloid Cells Are Enriched in Tonsillar Crypts, Providing Insight into the Viral Tropism of Human Papillomavirus.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 viral 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 multiparameter immunofluorescence staining demonstrated that the tonsillar crypts are enriched with myeloid populations that co-express multiple canonical and noncanonical immune checkpoints, including PD-L1, CTLA-42021-01-01T00:00:00Z2021 Oct2026-05-31T02:12:57.727Z2025-02-19T01:22:16.727ZS-EPMC84910923430369910.1016/j.ajpath.2021.06.012