Tadalafil Induced Modulation of Immune Response in HNSCC
Tadalafil Induced Modulation of Immune Response in HNSCC
批准号:
7587610
负责人:
Joseph A Califano
金额:
$36.08万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-01-01 至 2010-12-31
关键词:
AffectAftercareApoptosisBiological AssayBiopsyCD4 Positive T LymphocytesCD8B1 geneCandidaCell CountCell physiologyCellsChromosomal InstabilityChronicCialisDataDelayed HypersensitivityElementsEnvironmentEventGenesGeneticHead and Neck Squamous Cell CarcinomaHead and neck structureHistologicITGAM geneImmuneImmune responseImmunityImmunohistochemistryImmunosuppressionImmunosuppressive AgentsImmunotherapeutic agentImpairmentIndividualInfiltrationInflammatory ResponseLaboratoriesLymphocyteMalignant - descriptorMeasuresMediatingModalityMolecularMyelogenousNitric OxideNitric Oxide SynthaseOncogenesPathway interactionsPatientsPeripheralPhenotypePopulationProcessProductionRandomizedReactionSamplingSeriesSignal TransductionSquamous cell carcinomaSuppressor-Effector T-LymphocytesT-Cell ActivationT-LymphocyteTetanusTreatment EfficacyTumor BurdenTumor Suppressor ProteinsTumor-DerivedUnited Statesadvanced diseaseanergyarginasebasecarcinogenesisgain of functionimmune functionindexinginhibitor/antagonistmagnetic beadsneoplastic cellphosphodiesterase Vpublic health relevanceresponsetadalafiltumor
中文摘要
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英文摘要
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.
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海外基金