Tadalafil Induced Modulation of Immune Response in HNSCC

描述（由申请方提供）：他达拉非诱导调节HNSCC头颈部鳞状细胞癌（HNSCC）的免疫应答，在美国每年影响超过40，000例患者，但晚期疾病的治愈率徘徊在50%左右。HNSCC患者表现出肿瘤细胞免疫识别的显著损伤，并且逃避免疫应答是HNSCC致癌的重要因素。我们实验室的初步数据表明，成熟的CD 11b +/GR 1+髓源性抑制细胞（MDSC）诱导抑制性表型，导致HNSCC中CD 4+和CD 8 + T细胞的肿瘤特异性T细胞无能，并且通过磷酸二酯酶5（PDE 5）抑制剂功能性消除MDSC可以恢复HNSCC患者淋巴细胞中的T细胞功能。本研究将检查他达拉非作为免疫抑制剂逆转HNSCC患者MDSC介导的T细胞功能抑制的候选资格。公共卫生相关性：头颈部鳞状细胞癌（HNSCC）的治愈率约为50%，免疫应答逃避是HNSCC致癌的重要因素。本研究将考察他达拉非作为免疫抑制剂逆转HNSCC患者T细胞功能抑制的候选资格。

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.