S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Biomedical Sciences (대학원 의과학과) Journal Papers (저널논문_의과학과)
Interleukin-10 attenuates tumour growth by inhibiting interleukin-6/signal transducer and activator of transcription 3 signalling in myeloid-derived suppressor cells
- Issue Date
- ELSEVIER IRELAND LTD
- Cancer Letters, Vol.381 No.1, pp. 156-164
- Interleukin-10 attenuates tumour growth by inhibiting interleukin-6/signal transducer and activator of transcription 3 signalling in myeloid-derived suppressor cells ; 복합학 ; Cancer ; Interleukin-6 ; Myeloid-derived suppressor cells ; Interleukin-10 ; Signal transducer and activator of transcription 3
- 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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