Tadalafil Induced Modulation of Immune Response in HNSCC

Johns Hopkins University, Baltimore MD

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Abstract

DESCRIPTION (provided by applicant): 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.