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.
Our understanding of T cell subsets in the human tumor microenvironment lags much behind the more comprehensive analyses of these cells in mouse autoimmune disease models. This deficiency significantly tempers our efforts toward understanding basic human T cell biology and the potential interaction between Th cell subsets and cancer cells including cancer stem cells. The application takes a comprehensive approach by combining basic immunological methods, genetic research, and clinical and comparative analyses to address the nature of immune regulation in the microenvironment of oropharyngeal cancer. The application is conceptually and applicably significant, and will generate novel insight into new approaches in cancer immune therapy.
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|Cui, Tracy X; Kryczek, Ilona; Zhao, Lili et al. (2013) Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2. Immunity 39:611-21|