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: In the next series, we immunohistochemically examined the recruitment of CD8+ TILs and NK cells that were essentially involved in tumor immunity. In HM-1-IDO-transplanted mice, the IDO-positive signals in tumor cells were confirmed within the disseminated tumors, whereas they were not observed in the HM-1-mock group (Fig. 3a). The number of CD8+ TILs and NK cells within the tumors was significantly reduced in the HM-1-IDO group, compared with that in the HM-1-mock group (Fig. 3b,c,e,f). These observations suggested that IDO overexpression could suppress the recruitment of CD8+ TILs and NK cells into the tumor microenvironment. In contrast, the number of α-SMA+ myofibroblasts in the tumor stroma was significantly increased in the HM-1-IDO group, compared to that in the HM-1-mock group (Fig. 3d,g).
Affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama, Japan.