Immune Regulation in the Microenvironment of Oropharyngeal Cancer

描述（由申请人提供）：慢性炎症可能导致肿瘤的发生、发展和转移。然而，确切的机制仍有待充分了解。近年来的研究表明，肿瘤生物学的一个重要组成部分是致癌变化的免疫效应，而局部炎症和免疫反应的质量和状态是控制癌变和癌症进展的关键因素。肿瘤微环境中免疫相互作用的机制是癌症免疫学中一个关键且研究不足的领域，它将对免疫治疗策略的成功产生重大影响。IL-17+CD4+ T （Th17）和IL-22+CD4+ T （Th22）细胞存在于口咽癌中。Th17和Th22细胞在人口咽癌中的性质尚不清楚。我们的初步研究表明，Th17和Th22亚群在口咽癌的情况下可能在功能和机制上有所不同。根据我们的初步数据，我们的具体目标是：目的1：验证我们的假设，即Th17细胞在口咽癌中具有干细胞特征；目的2：验证我们的假设，即Th17细胞从表观遗传学角度影响口咽癌免疫；目的3：验证我们的假设，即Th22细胞促进癌症的干性，Th17/Th22细胞影响口咽癌患者的预后。

DESCRIPTION (provided by applicant): Chronic inflammation may contribute to tumor initiation, progression and metastasis. However, the precise mechanism remains to be fully understood. Recent studies indicate that an integral element of tumor biology is the immunologic effects of oncogenic changes, and the quality and state of local inflammation and immune responses are crucial factors controlling carcinogenesis and cancer progression. Mechanisms of immune interactions within the tumor microenvironment are a critical and understudied area of cancer immunology that will impact significantly on the success of immunotherapeutic strategies. IL-17+CD4+ T (Th17) and IL-22+CD4+ T (Th22) cells are found in oropharyngeal cancer. The nature of Th17 and Th22 cells is poorly understood in human oropharyngeal cancer. Our preliminary studies have demonstrated that Th17 and Th22 subsets may be functionally and mechanistically different in the context of oropharygeal cancer. Based on our preliminary data, our specific aims are: Aim 1: To test our hypothesis that Th17 cells have stem cell feature in oropharyngeal cancer Aim 2: To test our hypothesis that Th17 cells epigenetically impact oropharyngeal cancer immunity Aim 3: To test our hypothesis that Th22 cells promote cancer stemness, and Th17/Th22 cells affect patient outcome in oropharyngeal cancer.