Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment.
Bottom Line: This tumor-progressive effect was coincident with significantly reduced numbers of CD8(+) T cells and natural killer cells within tumors as well as increased levels of transforming growth factor-β and interleukin-10 in ascites.Finally, treatment with the IDO inhibitor 1-methyl-tryptophan significantly suppressed tumor dissemination and ascites with reduced transforming growth factor-β secretion.These findings showed that tumor-derived IDO promotes the peritoneal dissemination of ovarian cancer through suppression of tumor-infiltrating effector T cell and natural killer cell recruitment and reciprocal enhancement of immunosuppressive cytokines in ascites, creating an immunotolerogenic environment within the peritoneal cavity.
Affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama, Japan.Show MeSH
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Mentions: Because the levels of TGF-β and IL-10 in the ascites were significantly higher in HM-1-IDO-transplanted mice than in HM-1-mock-transplanted ones, we examined whether TGF-β and IL-10 could affect the proliferation and migration of HM-1 cells in vitro. Transforming growth factor-β enhanced the cell migratory activity in HM-1-parental, HM-1-mock, and HM-1-IDO cells to similar extents, whereas IL-10 had no significant effects on cell migration (Fig. 5). Neither TGF-β nor IL-10 showed significant effects on the proliferative activity of these cells (data not shown).
Affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama, Japan.