Expression profile and in vitro blockade of programmed death-1 in human papillomavirus-negative head and neck squamous cell carcinoma

Head Neck. 2015 Aug;37(8):1088-95. doi: 10.1002/hed.23706. Epub 2014 Sep 16.

Abstract

Background: Treatment with a blocking programmed death-1 (αPD-1) antibody recently showed clinical efficacy for various tumor types. In this study, we characterized the expression profile of PD-1/programmed death-ligand-1 (PD-L1) and the potential of PD-1 blockade in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC).

Methods: Lymphocytes from peripheral blood, draining lymph nodes, and the tumor were phenotyped for PD-1 expression, and their proliferative activity was assessed in the presence of blocking αPD-1 treatment. Primary tumor expression of PD-L1 was also analyzed using immunohistochemistry (IHC).

Results: Lymphocyte PD-1 expression was abundant with highest expression in the tumor, and in vitro mixed lymphocyte reaction demonstrated that PD-1 blockade could induce T cell proliferation. Furthermore, tumor cells were found to have 3 distinct patterns of PD-L1 expression with over 78% of the specimens demonstrating strong PD-L1 positivity.

Conclusion: Our data strongly supports the use of αPD-1 blockade in patients with HPV-negative HNSCC that are refractory to standard treatments.

Keywords: T cell; anergy; head and neck squamous cell carcinoma (HNSCC); immunotherapy; programmed death-1 (PD-1).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / immunology*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology*
  • CD4 Antigens / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / virology
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / immunology*
  • Head and Neck Neoplasms / virology
  • Humans
  • In Vitro Techniques / methods
  • Papillomaviridae*
  • Phenotype
  • Predictive Value of Tests
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / immunology*
  • Sensitivity and Specificity
  • Transcriptome
  • Tumor Cells, Cultured

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • CD4 Antigens
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor