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Interleukin-10 attenuates tumour growth by inhibiting interleukin-6/signal transducer and activator of transcription 3 signalling in myeloid-derived suppressor cells

Cited 13 time in Web of Science Cited 13 time in Scopus
Authors
Lee, Bo-Ra; Kwon, Bo-Eun; Hong, Eun-Hye; Shim, Aeri; Song, Jae-Hyoung; Kim, Hong-Min; Chang, Sun-Young; Kim, Yeon-Jeong; Kweon, Mi-Na; Youn, Je-In; Ko, Hyun-Jeong
Issue Date
2016-10
Publisher
ELSEVIER IRELAND LTD
Citation
Cancer Letters, Vol.381 No.1, pp. 156-164
Keywords
Interleukin-10 attenuates tumour growth by inhibiting interleukin-6/signal transducer and activator of transcription 3 signalling in myeloid-derived suppressor cells복합학CancerInterleukin-6Myeloid-derived suppressor cellsInterleukin-10Signal transducer and activator of transcription 3
Abstract
Interleukin-10 (IL-10) is a well-characterized anti-inflammatory cytokine, but its role in anti-cancer immunity is controversial. After injection with TC-1 cancer cells, we observed more rapid tumour growth and significantly higher interleukin-6 (IL-6) production in IL-10 knockout (IL-10(-/-)) mice than wild-type (WT) mice. Blocking IL-6 with an anti-IL-6 receptor (IL-6R) monoclonal antibody (mAb) inhibited tumour growth and myeloid-derived suppressor cell (MDSC) generation, which were significantly increased in IL-10-deficient mice. MDSCs and tumour cells from IL-10(-/-) mice had increased phosphorylated signal transducer and activator of transcription 3 (p-STAT3) levels. Treatment with a STAT3 inhibitor, S3I, reduced tumour growth, inhibited MDSC expansion, reduced IL-6 in tumours, and relieved T cell suppression. The combination of anti-IL-6R mAb and S3I further inhibited tumour growth compared to S3I treatment alone. These results suggested that the inhibition of the IL-6/STAT3 signalling axis is a candidate anti-cancer strategy, especially under systemic inflammatory conditions with high IL-6. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
ISSN
0304-3835
Language
English
URI
http://hdl.handle.net/10371/116933
DOI
https://doi.org/10.1016/j.canlet.2016.07.012
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Journal Papers (저널논문_의과학과)
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