Myeloid Cells Are Enriched in Tonsillar Crypts, Providing Insight into the Viral Tropism of Human Papillomavirus
| Autor: | Justin A. Bishop, William C. Faquin, Thomas J. Diefenbach, Yang Cheng, Darawan Rinchai, Austin Mattox, Jessica Roelands, Talia M. Saal, William H. Westra, Wouter Hendrickx, Mikael J. Pittet, Davide Bedognetti, Sara I. Pai, Alan E. Berger, Francesco M. Marincola, Geoffrey D. Young |
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| Rok vydání: | 2021 |
| Předmět: |
B7 Antigens
Myeloid Palatine Tonsil BTLA Laser Capture Microdissection Alphapapillomavirus Biology B7-H1 Antigen Epithelium Monocytes Pathology and Forensic Medicine Tonsillar crypts Antigens CD medicine Humans Myeloid Cells HPV infection Cancer Germinal center Regular Article Germinal Center Immune Checkpoint Proteins medicine.disease Viral Tropism medicine.anatomical_structure Head and Neck Neoplasms Tonsil Cancer research Tissue tropism Receptors Virus Transcriptome Cell Adhesion Molecules |
| Zdroj: | Am J Pathol |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2021.06.012 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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