| Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. | |
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MedLine Citation:
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PMID: 23288508 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Human papillomavirus-associated head and neck squamous cell carcinomas (HPV-HNSCC) originate in the tonsils, the major lymphoid organ that orchestrates immunity to oral infections. Despite its location, the virus escapes immune elimination during malignant transformation and progression. Here, we provide evidence for the role of the PD-1:PD-L1 pathway in HPV-HNSCC immune resistance. We demonstrate membranous expression of PD-L1 in the tonsillar crypts, the site of initial HPV infection. In HPV-HNSCCs that are highly infiltrated with lymphocytes, PD-L1 expression on both tumor cells and CD68+ tumor associated macrophages (TAMs) is geographically localized to sites of lymphocyte fronts, while the majority of CD8+ tumor infiltrating lymphocytes (TILs) express high levels of PD-1, the inhibitory PD-L1 receptor. Significant levels of mRNA for interferon-γ (IFN-γ, a major cytokine inducer of PD-L1 expression, were found in HPV+ PD-L1(+) tumors. Our findings support the role of the PD-1:PD-L1 interaction in creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance once tumors are established and suggest a rationale for therapeutic blockade of this pathway in patients with HPV-HNSCC. |
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Authors:
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Sofia Lyford-Pike; Shiwen Peng; Geoffrey D Young; Janis M Taube; William H Westra; Belinda Akpeng; Tullia C Bruno; Jeremy D Richmon; Hao Wang; Justin A Bishop; Lieping Chen; Charles G Drake; Suzanne L Topalian; Drew M Pardoll; Sara I Pai |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-3 |
Journal Detail:
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Title: Cancer research Volume: - ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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