Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma
| Autor: | Belinda Akpeng, Suzanne L. Topalian, Drew M. Pardoll, Jeremy D. Richmon, Janis M. Taube, Hao Wang, William H. Westra, Sara I. Pai, Tullia C. Bruno, Geoffrey D. Young, Sofia Lyford-Pike, Shiwen Peng, Justin A. Bishop, Lieping Chen, Charles G. Drake |
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| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Lymphocyte medicine.medical_treatment Programmed Cell Death 1 Receptor Biology CD8-Positive T-Lymphocytes B7-H1 Antigen Article Malignant transformation Interferon-gamma Tonsillar crypts PD-L1 medicine Humans Papillomaviridae Reverse Transcriptase Polymerase Chain Reaction medicine.disease Flow Cytometry Head and neck squamous-cell carcinoma Immunohistochemistry medicine.anatomical_structure Lymphatic system Cytokine Oncology Head and Neck Neoplasms Immunology biology.protein Carcinoma Squamous Cell CD8 |
| Zdroj: | Cancer research. 73(6) |
| ISSN: | 1538-7445 |
| Popis: | 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. Cancer Res; 73(6); 1733–41. ©2012 AACR. |
| Databáze: | OpenAIRE |
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