Tadalafil Induced Modulation of Immune Response in HNSCC

他达拉非诱导 HNSCC 免疫反应的调节

• 批准号: 7587610
• 负责人: Joseph A Califano
• 金额: $ 36.08万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7587610
• 关键词: Affect; Aftercare; Apoptosis; Biological Assay; Biopsy; CD4 Positive T Lymphocytes; CD8B1 gene; Candida; Cell Count; Cell physiology; Cells; Chromosomal Instability; Chronic; Cialis; Data; Delayed Hypersensitivity; Elements; Environment; Event; Genes; Genetic; Head and Neck Squamous Cell Carcinoma; Head and neck structure; Histologic; ITGAM gene; Immune; Immune response; Immunity; Immunohistochemistry; Immunosuppression; Immunosuppressive Agents; Immunotherapeutic agent; Impairment; Individual; Infiltration; Inflammatory Response; Laboratories; Lymphocyte; Malignant - descriptor; Measures; Mediating; Modality; Molecular; Myelogenous; Nitric Oxide; Nitric Oxide Synthase; Oncogenes; Pathway interactions; Patients; Peripheral; Phenotype; Population; Process; Production; Randomized; Reaction; Sampling; Series; Signal Transduction; Squamous cell carcinoma; Suppressor-Effector T-Lymphocytes; T-Cell Activation; T-Lymphocyte; Tetanus; Treatment Efficacy; Tumor Burden; Tumor Suppressor Proteins; Tumor-Derived; United States; advanced disease; anergy; arginase; base; carcinogenesis; gain of function; immune function; indexing; inhibitor/antagonist; magnetic beads; neoplastic cell; phosphodiesterase V; public health relevance; response; tadalafil; tumor

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.

描述（由申请人提供）：他达拉非诱导 HNSCC 免疫反应调节 在美国，头颈鳞状细胞癌 (HNSCC) 每年影响超过 40,000 人，但晚期疾病的治愈率徘徊在 50% 左右。 HNSCC 患者对肿瘤细胞的免疫识别能力显着受损，而逃避免疫反应是 HNSCC 癌变的一个重要因素。我们实验室的初步数据表明，成熟的 CD11b+/GR1+ 骨髓源性抑制细胞 (MDSC) 诱导抑制表型，导致 HNSCC 中 CD4+ 和 CD8+ T 细胞的肿瘤特异性 T 细胞无反应性，并且通过磷酸二酯酶 5 (PDE5) 抑制剂功能性消除 MDSC 可以恢复 HNSCC 中的 T 细胞功能。 来自 HNSCC 患者的淋巴细胞。本研究将检验他达拉非作为免疫治疗剂的候选资格，以逆转 HNSCC 患者中 MDSC 介导的 T 细胞功能抑制。公众健康相关性：头颈鳞状细胞癌 (HNSCC) 的治愈率约为 50%，而逃避免疫反应是 HNSCC 癌变的一个重要因素。本研究将检验他达拉非作为免疫治疗剂逆转 HNSCC 患者 T 细胞功能抑制的候选资格。