title: Interleukin-10 attenuates tumour growth by inhibiting interleukin-6/signal transducer and activator of transcription 3 signalling in myeloid-derived suppressor cells.
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.
authors.affiliation: Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341, South Korea.
authors.forename: Bo-Ra
authors.initials: BR
authors.lastname: Lee
authors.affiliation: Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341, South Korea.
authors.forename: Bo-Eun
authors.initials: BE
authors.lastname: Kwon
authors.affiliation: Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341, South Korea.
authors.forename: Eun-Hye
authors.initials: EH
authors.lastname: Hong
authors.affiliation: Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341, South Korea.
authors.forename: Aeri
authors.initials: A
authors.lastname: Shim
authors.affiliation: Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341, South Korea.
authors.forename: Jae-Hyoung
authors.initials: JH
authors.lastname: Song
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, South Korea.
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Ajou University, Suwon 16499, South Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Chang
authors.affiliation: College of Pharmacy, Inje University, Gimhae 50834, South Korea.
authors.forename: Yeon-Jeong
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Mucosal Immunology Lab., Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul 05505, South Korea.
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
authors.affiliation: Wide River Institute of Immunology, Seoul National University College of Medicine, Hongcheon 25159, South Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080 South Korea.
authors.forename: Je-In
authors.initials: JI
authors.lastname: Youn
authors.affiliation: Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341, South Korea. Electronic address: hjko@kangwon.ac.kr.
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Ko
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005838:Genotype; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072737:Myeloid-Derived Suppressor Cells / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D010766:Phosphorylation; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D047368:Tumor Burden; D019139:Tumor Escape; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; C556062:IL10 protein, mouse; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C577686:interleukin-6, mouse; D016753:Interleukin-10
keywords: Cancer; Interleukin-10; Interleukin-6; Myeloid-derived suppressor cells; Signal transducer and activator of transcription 3