Abstract
Tryptophan metabolism is important to induce immune tolerance in tumors. To date, 3 types of tryptophan-metabolizing enzymes have been identified: indoleamine 2,3-dioxygenase 1 and 2 (IDO1 and IDO2) and tryptophan 2,3-dioxygenase 2. Numerous studies have focused on IDO1 as its expression is enhanced in various cancers. Recently, IDO2 has been identified as a tryptophan-metabolizing enzyme that is involved in several immune functions and expressed in cancers such as pancreatic cancer. However, the biological role of IDO2 in the induction of immune tolerance in tumors has not yet been reported. In the present study, we examined the effects of Ido2 depletion on tumor growth in a mouse model of Lewis lung carcinoma by using Ido2-knockout mice. Ido2-knockout mice had reduced tumor volumes compared to WT mice. Furthermore, Ido2 depletion altered the tumor microenvironment, such as tryptophan accumulation and kynurenine reduction, leading to enhancement of immune cell invasion. Finally, enzyme-linked immunospot assay revealed that Ido2 depletion enhanced γ-interferon secretion in the tumor. In conclusion, Ido2 is an important immune regulator in the tumor microenvironment. Our data indicate that IDO2 is a potential target for cancer treatment and drug development.
| Original language | English |
|---|---|
| Pages (from-to) | 3061-3067 |
| Number of pages | 7 |
| Journal | Cancer science |
| Volume | 110 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 01-10-2019 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
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Indoleamine 2,3-dioxygenase 2 depletion suppresses tumor growth in a mouse model of Lewis lung carcinoma. / Yamasuge, Wakana; Yamamoto, Yasuko; Fujigaki, Hidetsugu; Hoshi, Masato; Nakamoto, Kentaro; Kunisawa, Kazuo; Mouri, Akihiro; Nabeshima, Toshitaka; Saito, Kuniaki.
In: Cancer science, Vol. 110, No. 10, 01.10.2019, p. 3061-3067.Research output: Contribution to journal › Article
TY - JOUR
T1 - Indoleamine 2,3-dioxygenase 2 depletion suppresses tumor growth in a mouse model of Lewis lung carcinoma
AU - Yamasuge, Wakana
AU - Yamamoto, Yasuko
AU - Fujigaki, Hidetsugu
AU - Hoshi, Masato
AU - Nakamoto, Kentaro
AU - Kunisawa, Kazuo
AU - Mouri, Akihiro
AU - Nabeshima, Toshitaka
AU - Saito, Kuniaki
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Tryptophan metabolism is important to induce immune tolerance in tumors. To date, 3 types of tryptophan-metabolizing enzymes have been identified: indoleamine 2,3-dioxygenase 1 and 2 (IDO1 and IDO2) and tryptophan 2,3-dioxygenase 2. Numerous studies have focused on IDO1 as its expression is enhanced in various cancers. Recently, IDO2 has been identified as a tryptophan-metabolizing enzyme that is involved in several immune functions and expressed in cancers such as pancreatic cancer. However, the biological role of IDO2 in the induction of immune tolerance in tumors has not yet been reported. In the present study, we examined the effects of Ido2 depletion on tumor growth in a mouse model of Lewis lung carcinoma by using Ido2-knockout mice. Ido2-knockout mice had reduced tumor volumes compared to WT mice. Furthermore, Ido2 depletion altered the tumor microenvironment, such as tryptophan accumulation and kynurenine reduction, leading to enhancement of immune cell invasion. Finally, enzyme-linked immunospot assay revealed that Ido2 depletion enhanced γ-interferon secretion in the tumor. In conclusion, Ido2 is an important immune regulator in the tumor microenvironment. Our data indicate that IDO2 is a potential target for cancer treatment and drug development.
AB - Tryptophan metabolism is important to induce immune tolerance in tumors. To date, 3 types of tryptophan-metabolizing enzymes have been identified: indoleamine 2,3-dioxygenase 1 and 2 (IDO1 and IDO2) and tryptophan 2,3-dioxygenase 2. Numerous studies have focused on IDO1 as its expression is enhanced in various cancers. Recently, IDO2 has been identified as a tryptophan-metabolizing enzyme that is involved in several immune functions and expressed in cancers such as pancreatic cancer. However, the biological role of IDO2 in the induction of immune tolerance in tumors has not yet been reported. In the present study, we examined the effects of Ido2 depletion on tumor growth in a mouse model of Lewis lung carcinoma by using Ido2-knockout mice. Ido2-knockout mice had reduced tumor volumes compared to WT mice. Furthermore, Ido2 depletion altered the tumor microenvironment, such as tryptophan accumulation and kynurenine reduction, leading to enhancement of immune cell invasion. Finally, enzyme-linked immunospot assay revealed that Ido2 depletion enhanced γ-interferon secretion in the tumor. In conclusion, Ido2 is an important immune regulator in the tumor microenvironment. Our data indicate that IDO2 is a potential target for cancer treatment and drug development.
UR - http://www.scopus.com/inward/record.url?scp=85072994444&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072994444&partnerID=8YFLogxK
U2 - 10.1111/cas.14179
DO - 10.1111/cas.14179
M3 - Article
C2 - 31444833
AN - SCOPUS:85072994444
VL - 110
SP - 3061
EP - 3067
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 10
ER -