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Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 suppresses tumor growth in breast cancer-bearing mice by negatively regulating myeloid-derived suppressor cell functions

Authors
Hong, Hye-JinLim, Hui XuanSong, Ju HanLee, ArimKim, EugeneCho, DaehoCohen, Edward P.Kim, Tae Sung
Issue Date
Jan-2016
Publisher
Springer Science and Business Media Deutschland GmbH
Keywords
AIMP1; Myeloid-derived suppressor cells; Breast cancer; T cells; Mice
Citation
CANCER IMMUNOLOGY, IMMUNOTHERAPY, v.65, no.1, pp 61 - 72
Pages
12
Journal Title
CANCER IMMUNOLOGY, IMMUNOTHERAPY
Volume
65
Number
1
Start Page
61
End Page
72
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/3589
DOI
10.1007/s00262-015-1777-2
ISSN
0340-7004
1432-0851
Abstract
Myeloid-derived suppressor cells (MDSCs) are one of the most important cell types that contribute to negative regulation of immune responses in the tumor microenvironment. Recently, aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1), a novel pleiotropic cytokine, was identified as an antitumor protein that inhibits angiogenesis and induces antitumor responses. However, the effect of AIMP1 on MDSCs in the tumor environment remains unclear. In the present study, we demonstrated that AIMP1 significantly inhibited tumor growth in 4T1 breast cancer-bearing mice and reduced MDSCs population of tumor sites and spleens of tumor-bearing mice. AIMP1 reduced expansion of MDSCs from bone marrow-derived cells in the tumor-conditioned media. AIMP1 also negatively regulated suppressive activities of MDSCs by inhibiting IL-6 and NO production, and Arg-1 expression. Furthermore, treatment of breast cancer-bearing mice with AIMP1 decreased the capacity of MDSCs to suppress T cell proliferation and Treg cell induction. Western blot and inhibition experiments showed that downregulation of MDSCs functions by AIMP1 may result from attenuated activation of STATs, Akt, and ERK. These findings indicate that AIMP1 plays an essential role in negative regulation of suppressive functions of MDSCs. Therefore, it has a significant potential as a therapeutic agent for cancer treatment.
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