Open AccessIndoleamine 2,3‐dioxygenase 2 depletion suppresses tumor growth in a mouse model of Lewis lung carcinoma
Author(s) -
Yamasuge Wakana,
Yamamoto Yasuko,
Fujigaki Hidetsugu,
Hoshi Masato,
Nakamoto Kentaro,
Kunisawa Kazuo,
Mouri Akihiro,
Nabeshima Toshitaka,
Saito Kuniaki
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14179
Subject(s) - indoleamine 2,3 dioxygenase , immune system , kynurenine , tumor microenvironment , cancer research , biology , lewis lung carcinoma , immunology , tryptophan metabolism , immune tolerance , cancer , tryptophan , metastasis , biochemistry , genetics , amino acid
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 ( IDO 1 and IDO 2) and tryptophan 2,3‐dioxygenase 2. Numerous studies have focused on IDO 1 as its expression is enhanced in various cancers. Recently, IDO 2 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 IDO 2 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 IDO 2 is a potential target for cancer treatment and drug development.