Journal
CANCER LETTERS
Volume 381, Issue 1, Pages 156-164Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.07.012
Keywords
Cancer; Interleukin-6; Myeloid-derived suppressor cells; Interleukin-10; Signal transducer and activator of transcription 3
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Funding
- Basic Science Research Program through National Research Foundation (NRF) - Ministry of Science, ICT and Future Planning of Korea [NRF-2014R1A2A2A01002576]
- Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [HI15C0450]
- National Research Foundation of Korea [2014R1A2A2A01002576, 22A20130012667] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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