Type I interferons exert anti-tumor effect via reversing immunosuppression mediated by mesenchymal stromal cells

• DOI: 10.1038/onc.2016.128
• Publication Date: 2016-04-25T10:04:44Z
• Authors: P Shou; Q Chen; J Jiang; C Xu; J Zhang; C Zheng; M Jiang; T Velletri; W Cao; Y Huang; Q Yang; X Han; L Zhang; L Wei; A B Rabson; Y E Chin; Y Wang; Y Shi
• Keywords: STAT1

Mesenchymal stromal cells (MSCs) are strongly immunosuppressive via producing nitric oxide (NO) and known to migrate into tumor sites promote growth, but the underlying mechanisms remain largely elusive. Here, we found that interferon alpha (IFNα)-secreting MSCs showed more dramatic inhibition effect on progression than of IFNα alone. Interestingly, IFNα-primed could also effectively suppress growth. Mechanistically, demonstrated both IFNβ (type I IFNs) reversed splenocyte proliferation. This type IFNs was exerted through inhibiting inducible NO synthase (iNOS) expression in IFNγ TNFα-stimulated MSCs. Notably, only production inhibited by IFNα; other cytokines or chemokines tested not suppressed. Furthermore, promoted switch from signal transducer activator transcription 1 (Stat1) homodimers Stat1-Stat2 heterodimers. Studies using luciferase reporter system chromatin immunoprecipitation assay revealed suppressed iNOS binding Stat1 promoter. Therefore, synergistic anti-tumor effects were achieved production. study provides essential information for understanding MSC-mediated immunosuppression development better clinical strategies cancer immunotherapy.