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


CONCLUSIONS
Our data strongly supports the use of αPD-1 blockade in patients with HPV-negative HNSCC that are refractory to standard treatments.
Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.|Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Ian-James
IJ
Malm
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Tullia C
TC
Bruno
Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Juan
J
Fu
Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Qi
Q
Zeng
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Janis M
JM
Taube
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
William
W
Westra
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Drew
D
Pardoll
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Charles G
CG
Drake
Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.|Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Young J
YJ
Kim
D060890:B7-H1 Antigen / Q000235:genetics / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006801:Humans; D066298:In Vitro Techniques / Q000379:methods; D027383:Papillomaviridae; D010641:Phenotype; D011237:Predictive Value of Tests; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology*; D012680:Sensitivity and Specificity; D059467:Transcriptome; D014407:Tumor Cells, Cultured
D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D015704:CD4 Antigens; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
T cell; anergy; head and neck squamous cell carcinoma (HNSCC); immunotherapy; programmed death-1 (PD-1)