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Abstract

adverse prognostic factor in ovarian cancer.6 It is known that inducible Tregs and Th17 cells share a reciprocal differentiation pathway from uncommitted CD4 precursors.4 In the current study, the authors show that macrophages isolated from ovarian tumors biased the in vitro differentiation of uncommitted CD4 T cells toward Th17 cells. Therefore, the observed inverse correlation between Th17 cells and Tregs in tumors may reflect differing conditions within different tumors, favoring either inflammation (Th17) or suppression (Tregs). Furthermore, the Th17 and Treg lineages have recently been shown to be rather more plastic than previously thought, with several studies suggesting the possibility of interconversion between the 2 lineages.7 Thus, the inverse relationship between Th17 cells and Tregs observed in ovarian cancers may be more than simply a descriptive association. It may reflect fundamental differences in the nature of the spontaneous antitumor immune response—differences that appear to have significant impact on patient survival. Finally, the Th17 cells in ovarian cancers were found to simultaneously express high levels of multiple other proinflammatory effector cytokines (IL-2, TNF, IFN) in addition to IL-17 (panel B in the figure). In other settings, this so-called polyfunctional pattern of effector cytokine production has been associated with robust CD4 response to infection and vaccination.8 Other investigators, including myself, have reported similar polyfunctional cytokine response by Th17like cells in mouse tumor models as well.9 Thus, taken together, Kryczek et al have described a functionally important and hitherto unrecognized population of CD4 T cells in ovarian cancers that favor enhanced inflammatory responses and reduced Treg-mediated suppression. The presence of these polyfunctional Th17 cells was statistically associated with better clinical outcome. This raises the question of whether a similar population could be therapeutically induced or expanded (eg, by vaccines or other active immunotherapy), and if this would likewise result in improved patient outcome. Conflict-of-interest disclosure: The author declares no competing financial interests. ■