%0 Journal Article
%T The Multifaceted Role of Th17 Lymphocytes and Their Associated Cytokines in Cancer
%A Darya Alizadeh
%A Emmanuel Katsanis
%A Nicolas Larmonier
%J Journal of Immunology Research
%D 2013
%R 10.1155/2013/957878
%X While the role of T helper 17 lymphocytes (Th17) in the pathogenesis of autoimmune diseases and in infectious immunity has been relatively well defined, the impact of these cells and their associated cytokines on cancer development is still under debate. Although multiple reports have indicated that Th17 can promote anticancer immunity, others have argued that these cells may exhibit tumor-promoting properties. This dichotomy in the function of Th17 lymphocytes in cancer may be related to the versatile nature of these cells, being capable of differentiating into either proinflammatory Th1 or suppressive FoxP3-expressing Treg cells or hybrid T cell subsets depending on the underlying environmental conditions. In the current review, we examine the role of Th17 lymphocytes and Th17-associated cytokines in cancer and discuss how factors that control their final lineage commitment decision may influence the balance between their tumor-promoting versus tumor-suppressing properties. 1. Introduction CD4+ T helper (Th) lymphocytes are essential for the regulation of immune responses as they are endowed with the ability to modulate the function of CD8+ cytotoxic T lymphocytes (CTLs) [1, 2], B cells [3], NK cells [4], macrophages, and dendritic cells [5, 6]. Following triggering of their T cell receptor (TCR) and in the presence of appropriate costimulatory signals and specific cytokines, na£żve CD4+ T lymphocytes differentiate into various effector or regulatory cells characterized by distinct functions and specific cytokine production profiles. For many years, it was believed that the expression of two mutually exclusive differentiation programs led to the polarization of na£żve CD4+ T cells towards either Th1 or Th2 lymphocytes [7, 8]. Terminally differentiated Th1 cells are characterized by the expression of the transcription factor Tbet and the production of IFN [9]. Th1 activate CTLs, macrophages and are required for the elimination of intracellular pathogens [7, 10]. Th1 cell lineage commitment is primarily triggered by IFN and IL-12 [11, 12]. Th2 lymphocytes, defined by transcription factor GATA3 expression and the secretion of IL-4, IL-5, IL-10, and IL-13, play an essential role in B cell-mediated humoral responses against extracellular pathogens and can inhibit Th1-dependent cellular immunity [13¨C15]. More recently, several subsets of CD4+ T cells exhibiting immunosuppressive activity have been described (extensively reviewed elsewhere [16¨C21]). These so-called regulatory T lymphocytes (Tregs) may be generated during T cell development in the thymus
%U http://www.hindawi.com/journals/jir/2013/957878/