Interleukin-10 attenuates tumour growth by inhibiting interleukin-6/signal transducer and activator of transcription 3 signalling in myeloid-derived suppressor cells
| Autor: | Bo-Eun Kwon, Hyun-Jeong Ko, Aeri Shim, Je-In Youn, Hong-Min Kim, Jae-Hyoung Song, Yeon-Jeong Kim, Sun-Young Chang, Bo Ra Lee, Mi-Na Kweon, Eun-Hye Hong |
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| Rok vydání: | 2016 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine Cancer Research Time Factors Genotype T-Lymphocytes medicine.medical_treatment T cell Uterine Cervical Neoplasms 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Animals Phosphorylation STAT3 Cell Proliferation Mice Knockout biology Interleukin-6 Myeloid-Derived Suppressor Cells Antibodies Monoclonal Receptors Interleukin-6 Molecular biology Interleukin-10 Tumor Burden Mice Inbred C57BL Interleukin 10 Phenotype 030104 developmental biology Cytokine medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer cell STAT protein Myeloid-derived Suppressor Cell biology.protein Female Tumor Escape Signal Transduction |
| Zdroj: | Cancer Letters. 381:156-164 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2016.07.012 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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