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: Finally, we investigated the therapeutic potential of 1-MT, a specific IDO inhibitor, using the same mouse model of peritoneal carcinomatosis. On day 14 after tumor injection, the 1-MT treatment significantly suppressed the tumor volume and ascites accumulation compared with those in the untreated (vehicle alone) group (Fig. 6a,b). In parallel with decreased tumor dissemination, the TGF-β level in ascites was significantly reduced in the 1-MT treatment group compared with that in the untreated group (Fig. 6c). There was no significant difference in IL-10 levels between the two groups (data not shown).
Affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama, Japan.