Tadalafil induced modulation of immune response in HNSCC Head and neck squamous cell carcinoma (HNSCC) affects over 40,000 individuals per year in the United States, however cure rates for advanced disease hover around 50%. HNSCC patients demonstrate significant impairment in immune recognition of tumor cells, and evasion from immune response is a significant factor in HNSCC carcinogenesis. Preliminary data from our laboratory suggest that mature CD11b+/GR1+ myeloid derived suppressor cells (MDSC)s induce a suppressive phenotype resulting in tumor-specific T cell anergy in both CD4+ and CD8+ T-cells in HNSCC, and that functional elimination of MDSCs via phosphodiesterase 5 (PDE5) inhibitors can restore T cell function in lymphocytes from HNSCC patients. This study will examine the candidacy of tadalafil as an immunotherapeutic agent to reverse MDSC mediated suppression of T cell function in patients with HNSCC.

Public Health Relevance

Head and neck squamous cell carcinoma (HNSCC)is associated with cure rate of approximately 50% and evasion from immune response is a significant factor in HNSCC carcinogenesis. This study will examine the candidacy of tadalafil as an immunotherapeutic agent to reverse suppression of T cell function in patients with HNSCC.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA135635-01A1
Application #
7587610
Study Section
Clinical Oncology Study Section (CONC)
Program Officer
Timmer, William C
Project Start
2009-01-01
Project End
2010-12-31
Budget Start
2009-01-01
Budget End
2009-12-31
Support Year
1
Fiscal Year
2009
Total Cost
$360,800
Indirect Cost
Name
Johns Hopkins University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Califano, Joseph A; Khan, Zubair; Noonan, Kimberly A et al. (2015) Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma. Clin Cancer Res 21:30-8
Hennessey, P T; Westra, W H; Califano, J A (2009) Human papillomavirus and head and neck squamous cell carcinoma: recent evidence and clinical implications. J Dent Res 88:300-6