Myeloid Cells Are Enriched in Tonsillar Crypts, Providing Insight into the Viral Tropism of Human Papillomavirus

Austin K. Mattox, Jessica Roelands, Talia M. 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, Sara I. Pai

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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-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.

Original languageEnglish (US)
Pages (from-to)1774-1786
Number of pages13
JournalAmerican Journal of Pathology
Issue number10
StatePublished - Oct 2021

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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