Indoleamine 2,3-dioxygenase 2 depletion suppresses tumor growth in a mouse model of Lewis lung carcinoma

Wakana Yamasuge, Yasuko Yamamoto, Hidetsugu Fujigaki, Masato Hoshi, Kentaro Nakamoto, Kazuo Kunisawa, Akihiro Mouri, Toshitaka Nabeshima, Kuniaki Saito

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)3061-3067
Number of pages7
JournalCancer science
Volume110
Issue number10
DOIs
Publication statusPublished - 01-10-2019

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Lewis Lung Carcinoma
Tryptophan
Growth
Neoplasms
Immune Tolerance
Tumor Microenvironment
Knockout Mice
Tryptophan Oxygenase
Kynurenine
Enzyme-Linked Immunospot Assay
Enzymes
Tumor Burden
Pancreatic Neoplasms
Interferons

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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title = "Indoleamine 2,3-dioxygenase 2 depletion suppresses tumor growth in a mouse model of Lewis lung carcinoma",
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.",
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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 journalArticle

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

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