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Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment.

Tanizaki Y, Kobayashi A, Toujima S, Shiro M, Mizoguchi M, Mabuchi Y, Yagi S, Minami S, Takikawa O, Ino K - Cancer Sci. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama, Japan.

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Therapeutic effects of 1-methyl-tryptophan 1-MT on tumor progression in mice. Mice transplanted with indoleamine 2,3-dioxygenase-overexpressing murine ovarian carcinoma OV2944-HM-1 cells (HM-1-IDO) were treated with 1-MT three times weekly. On day 14, tumor volume (a), ascites volume (b), and the level of transforming growth factor-β (TGF-β) in ascites (c) were evaluated. All values represent mean ± SD. *P < 0.05, vehicle versus 1-MT.
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fig06: Therapeutic effects of 1-methyl-tryptophan 1-MT on tumor progression in mice. Mice transplanted with indoleamine 2,3-dioxygenase-overexpressing murine ovarian carcinoma OV2944-HM-1 cells (HM-1-IDO) were treated with 1-MT three times weekly. On day 14, tumor volume (a), ascites volume (b), and the level of transforming growth factor-β (TGF-β) in ascites (c) were evaluated. All values represent mean ± SD. *P < 0.05, vehicle versus 1-MT.

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).


Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment.

Tanizaki Y, Kobayashi A, Toujima S, Shiro M, Mizoguchi M, Mabuchi Y, Yagi S, Minami S, Takikawa O, Ino K - Cancer Sci. (2014)

Therapeutic effects of 1-methyl-tryptophan 1-MT on tumor progression in mice. Mice transplanted with indoleamine 2,3-dioxygenase-overexpressing murine ovarian carcinoma OV2944-HM-1 cells (HM-1-IDO) were treated with 1-MT three times weekly. On day 14, tumor volume (a), ascites volume (b), and the level of transforming growth factor-β (TGF-β) in ascites (c) were evaluated. All values represent mean ± SD. *P < 0.05, vehicle versus 1-MT.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317851&req=5

fig06: Therapeutic effects of 1-methyl-tryptophan 1-MT on tumor progression in mice. Mice transplanted with indoleamine 2,3-dioxygenase-overexpressing murine ovarian carcinoma OV2944-HM-1 cells (HM-1-IDO) were treated with 1-MT three times weekly. On day 14, tumor volume (a), ascites volume (b), and the level of transforming growth factor-β (TGF-β) in ascites (c) were evaluated. All values represent mean ± SD. *P < 0.05, vehicle versus 1-MT.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama, Japan.

Show MeSH
Related in: MedlinePlus