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    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
25112868 - Heme oxygenase-1 ameliorates dextran sulfate sodium-induced acute murine colitis by reg...
23250618 - Myeloid cell hif-1α regulates asthma airway resistance and eosinophil function.
25015278 - Toll-like receptor ligation for the induction of regulatory b cells.
24185508 - The role of mitochondrial dysfunction in sepsis-induced multi-organ failure.
17385278 - The killing of neurons by beta-amyloid peptides, prions, and pro-inflammatory cytokines.
9605108 - Hepatic inflammatory responses to alphaalpha-cross-linked hemoglobin infusion in rats.
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    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Antigens, CD274 / physiology*
CD8-Positive T-Lymphocytes / immunology
Carcinoma, Squamous Cell / immunology*,  virology
Flow Cytometry
Head and Neck Neoplasms / immunology*,  virology
Humans
Immunohistochemistry
Interferon-gamma / metabolism
Papillomaviridae / isolation & purification*
Programmed Cell Death 1 Receptor / physiology*
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
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
Chemical
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
Comments/Corrections

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


Previous Document:  Somatosensory Temporal Discrimination Threshold Is Increased in Patients with Cerebellar Atrophy.
Next Document:  ALX1 induces Snail expression to promote epithelial to mesenchymal transition and invasion of ovaria...