Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma

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

Research output: Contribution to journalArticle

423 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1733-1741
Number of pages9
JournalCancer Research
Volume73
Issue number6
DOIs
StatePublished - Mar 15 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma'. Together they form a unique fingerprint.

  • Cite this

    Lyford-Pike, S., Peng, S., Young, G. D., Taube, J. M., Westra, W. H., Akpeng, B., Bruno, T. C., Richmon, J. D., Wang, H., Bishop, J. A., Chen, L., Drake, C. G., Topalian, S. L., Pardoll, D. M., & Pai, S. I. (2013). Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Research, 73(6), 1733-1741. https://doi.org/10.1158/0008-5472.CAN-12-2384