Interleukin-10 attenuates tumour growth by inhibiting interleukin-6/signal transducer and activator of transcription 3 signalling in myeloid-derived suppressor cells. Issue 1 (10th October 2016)

• Record Type: Journal Article
• 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
• Is Part Of: Cancer letters. Volume 381:Issue 1(2016)
• Page Start: 156
• Page End: 164
• Publication Date: 2016-10-10
• Subjects: Cancer -- Interleukin-6 -- Myeloid-derived suppressor cells -- Interleukin-10 -- Signal transducer and activator of transcription 3; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.07.012
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: IL-10-deficiency accelerated tumour growth via the up-regulation of IL-6. IL-6R blockade and STAT3 inhibitor reduced tumour growth and MDSCs. STAT3 inhibitor attenuated MDSCs expansion and suppressed IL-6 overproduction in IL-10-deficient mice. 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.