title: 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.
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.
authors.affiliation: Department of Oncology, 174th Hospital of the Chinese People's Liberation Army, Affiliated Chenggong Hospital of Xiamen University, Xiamen, Fujian Province, People's Republic of China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.forename: Shengyu
authors.initials: S
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ding
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Ye
authors.forename: Yingyi
authors.initials: Y
authors.lastname: Xu
authors.forename: Huixiang
authors.initials: H
authors.lastname: He
authors.forename: Qiaozhen
authors.initials: Q
authors.lastname: Li
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Mi
authors.forename: Chunhua
authors.initials: C
authors.lastname: Guo
authors.forename: Zhicai
authors.initials: Z
authors.lastname: Lin
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Yaya
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Chen
authors.forename: Jianghua
authors.initials: J
authors.lastname: Yan
mesh_terms: D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000276:immunology*; D051940:B7-2 Antigen / Q000096:biosynthesis; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007155:Immunologic Factors / Q000378:metabolism; D016130:Immunophenotyping; D053614:Janus Kinase 2 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009842:Oligopeptides / Q000378:metabolism; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000037:antagonists & inhibitors*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015854:Up-Regulation; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D051940:B7-2 Antigen; D016207:Cytokines; D007136:Immunoglobulins; D007155:Immunologic Factors; D053614:Janus Kinase 2; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000097802:CD83 Antigen; C497964:CD86 protein, human; C108944:SOCS1 protein, human; C507924:JAK2 protein, human