Document Detail

Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma.
MedLine Citation:
PMID:  23288508     Owner:  NLM     Status:  MEDLINE    
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 show 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 is geographically localized to sites of lymphocyte fronts, whereas the majority of CD8+ tumor-infiltrating lymphocytes express high levels of PD-1, the inhibitory PD-L1 receptor. Significant levels of mRNA for 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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-03
Journal Detail:
Title:  Cancer research     Volume:  73     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-18     Completed Date:  2013-08-05     Revised Date:  2014-03-26    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1733-41     Citation Subset:  IM    
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MeSH Terms
Antigens, CD274 / physiology*
CD8-Positive T-Lymphocytes / immunology
Carcinoma, Squamous Cell / immunology*,  virology
Flow Cytometry
Head and Neck Neoplasms / immunology*,  virology
Interferon-gamma / metabolism
Papillomaviridae / isolation & purification*
Programmed Cell Death 1 Receptor / physiology*
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
P50 DE019032/DE/NIDCR NIH HHS; P50 DE019032/DE/NIDCR NIH HHS; R01 CA142779/CA/NCI NIH HHS; R01 CA142779/CA/NCI NIH HHS; T32 AI007247/AI/NIAID NIH HHS; T32000027//PHS HHS
Reg. No./Substance:
0/Antigens, CD274; 0/CD274 protein, human; 0/PDCD1 protein, human; 0/Programmed Cell Death 1 Receptor; 82115-62-6/Interferon-gamma

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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