TY - JOUR
T1 - Inhibition of indoleamine 2,3-dioxygenase suppresses NK cell activity and accelerates tumor growth
AU - Kai, Seiichiro
AU - Goto, Shigeru
AU - Tahara, Kouichirou
AU - Sasaki, Atsushi
AU - Kawano, Katsunori
AU - Kitano, Seigo
PY - 2003/11
Y1 - 2003/11
N2 - Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolizing enzyme, is induced under various pathological conditions, including viral and bacterial infection, allograft rejection, cerebral ischemia, and tumor growth. We have previously reported that the expression of IDO mRNA was increased in some clinical cases of hepatocellular carcinoma in which the recurrence-free survival rate in these IDO-positive patients was significantly higher than that in patients without IDO mRNA induction in tumors. Additionally, IDO expressed in tumors was localized not to the tumor cells but instead to tumor-infiltrating cells by immunohistochemistry. In this study, in order to elucidate the mechanisms underlying anti-tumor effect of IDO, we investigated whether IDO inhibitor (1-methyl-dl-tryptophan, 1MT) affects the growth of subcutaneous B16 tumors in mice. Subsequently, the activity of natural killer (NK) cells was investigated under the conditions of inhibited IDO activity in vivo and in vitro. IDO mRNA expression of B16 cells, B16 subcutaneous tumor, sprenocytes of mice, and human NK cells were studied by reverse transcription-polymerase chain reaction. B16 subcutaneous tumor growth with or without IDO inhibition was observed and cytotoxic activity of NK cells were investigated under the conditions of inhibited IDO activity in vivo and in vitro. IDO mRNA was expressed in B16 subcutaneous tumor, splenocytes of tumor bearing mice, co-cultured splenocytes with B16, and human NK cells. On day 14, after injection of B16 melanoma cells, the sizes of tumors in IDO-inhibited mice were significantly larger than those in control mice. The cytotoxic activity of mice NK cells was reduced by IDO inhibition in vivo. In vitro inhibition of IDO, NK activity was reduced in dose-dependent manner of 1 MT. In conclusion, these results indicated that IDO plays an important role in anti-tumor immunity by regulating cytotoxic activity of NK cells.
AB - Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolizing enzyme, is induced under various pathological conditions, including viral and bacterial infection, allograft rejection, cerebral ischemia, and tumor growth. We have previously reported that the expression of IDO mRNA was increased in some clinical cases of hepatocellular carcinoma in which the recurrence-free survival rate in these IDO-positive patients was significantly higher than that in patients without IDO mRNA induction in tumors. Additionally, IDO expressed in tumors was localized not to the tumor cells but instead to tumor-infiltrating cells by immunohistochemistry. In this study, in order to elucidate the mechanisms underlying anti-tumor effect of IDO, we investigated whether IDO inhibitor (1-methyl-dl-tryptophan, 1MT) affects the growth of subcutaneous B16 tumors in mice. Subsequently, the activity of natural killer (NK) cells was investigated under the conditions of inhibited IDO activity in vivo and in vitro. IDO mRNA expression of B16 cells, B16 subcutaneous tumor, sprenocytes of mice, and human NK cells were studied by reverse transcription-polymerase chain reaction. B16 subcutaneous tumor growth with or without IDO inhibition was observed and cytotoxic activity of NK cells were investigated under the conditions of inhibited IDO activity in vivo and in vitro. IDO mRNA was expressed in B16 subcutaneous tumor, splenocytes of tumor bearing mice, co-cultured splenocytes with B16, and human NK cells. On day 14, after injection of B16 melanoma cells, the sizes of tumors in IDO-inhibited mice were significantly larger than those in control mice. The cytotoxic activity of mice NK cells was reduced by IDO inhibition in vivo. In vitro inhibition of IDO, NK activity was reduced in dose-dependent manner of 1 MT. In conclusion, these results indicated that IDO plays an important role in anti-tumor immunity by regulating cytotoxic activity of NK cells.
KW - Anti-tumor immunity
KW - Indoleamine 2,3-dioxygenase
KW - Natural killer cell
KW - Tryptophan
UR - http://www.scopus.com/inward/record.url?scp=0347357866&partnerID=8YFLogxK
U2 - 10.1111/j.1533-869X.2003.01108.x
DO - 10.1111/j.1533-869X.2003.01108.x
M3 - 文章
C2 - 14678522
AN - SCOPUS:0347357866
SN - 1359-4117
VL - 3
SP - 336
EP - 345
JO - Journal of Experimental Therapeutics and Oncology
JF - Journal of Experimental Therapeutics and Oncology
IS - 6
ER -