A suppressor of cytokine signaling 1 antagonist enhances antigen-presenting capacity and tumor cell antigen-specific cytotoxic T lymphocyte responses by human monocyte-derived dendritic cells.

TitleA suppressor of cytokine signaling 1 antagonist enhances antigen-presenting capacity and tumor cell antigen-specific cytotoxic T lymphocyte responses by human monocyte-derived dendritic cells.
Publication TypeJournal Article
Year of Publication2013
AuthorsWang Y, Wang S, Ding Y, Ye Y, Xu Y, He H, Li Q, Mi Y, Guo C, Lin Z, Liu T, Zhang Y, Chen Y, Yan J
JournalClinical and vaccine immunology : CVI
Volume20
Issue9
Pagination1449-56
Date Published2013 Sep
Abstract

The suppressor of cytokine signaling 1 (SOCS1) has emerged as a critical inhibitory molecule for controlling the cytokine response and antigen presentation by dendritic cells (DCs), thereby regulating the magnitude of both innate and adaptive immunity. The aim of this study was to investigate whether the SOCS1 antagonist pJAK2(1001-1013) peptide can weaken or block the inhibition function of SOCS1 in DCs by evaluating the phenotype and cytokine production, antigen-presenting, and specific T-cell-activating capacities of DCs electroporated with human gastric cancer cell total RNA. Furthermore, STAT1 activation of the JAK/STAT signal pathway mediated by SOCS1 was analyzed by Western blotting. The results demonstrate that the SOCS1 antagonist pJAK2(1001-1013) peptide upregulated the expression of the maturation marker (CD83) and costimulatory molecule (CD86) of RNA-electroporated human monocyte-derived mature DCs (mDCs), potentiated the capacity of mDCs to induce T-cell proliferation, stimulated the secretion of proinflammatory cytokines, and enhanced the cytotoxicity of tumor cell antigen-specific CTLs activated by human gastric cancer cell total RNA-electroporated mDCs. Data from Western blot analysis indicate that STAT1 was further activated in pJAK2(1001-1013) peptide-loaded mDCs. These results imply that the SOCS1 antagonist pJAK2(1001-1013) peptide is an effective reagent for the enhancement of antigen-specific antitumor immunity by DCs.

DOI10.1128/JVI.01190-13
Alternate JournalClin. Vaccine Immunol.