A SOCS1 antagonist enhances antigen-presenting capacity and tumor

18 Suppressors of cytokine signaling (SOCS) has emerged as a critical inhibitory molecule for 19 controlling the cytokine response and antigen presentation by dendritic cells (DCs), thereby 20 regulating the magnitude of both innate and adaptive immunity. The aim of this study was to 21 investigate whether the SOCS1 antagonist pJAK2(1001–1013) peptide can weaken or block the 22 inhibition function of SOCS1 in DCs by evaluating the phenotype, cytokine production, 23 antigen-presenting and specific T-cell-activating capacity of DCs electroporated with human gastric 24 cancer cell total RNA. Furthermore, the STAT1 activation of JAK/STAT signal pathway mediated 25 by SOCS1 was analyzed by Western blot. Results demonstrated that the SOCS1 antagonist 26 pJAK2(1001–1013) peptide up-regulated the expression of the maturation marker (CD83) and 27 co-stimulatory molecule (CD86) of RNA-electroporated human monocyte-derived mature DCs 28 (mDCs), potentiated the capacity of mDCs to induce T-cell proliferation, stimulated the secretion of 29 pro-inflammatory cytokines, and enhanced the cytotoxicity of tumor cell antigen-specific CTLs 30 activated by human gastric cancer cell total RNA-electroporated mDCs. Data from Western blot 31 analysis indicated that STAT1 was further activated in pJAK2(1001–1013) peptide-loaded mDCs. 32 These results imply that the SOCS1 antagonist pJAK2(1001–1013) peptide is an effective reagent 33 to enhance antigen-specific antitumor immunity by DCs. 34