title: Immunosuppressive effect of bladder cancer on function of dendritic cells involving of Jak2/STAT3 pathway.
abstract: Function of dendritic cells (DCs) is impaired by some cancer cells. However, the effect of bladder cancer cell (BCC) on phenotype and function of DCs remains unclear. In this study, healthy human peripheral blood mononuclear cells (PBMCs) derived DCs were co-cultured with BCC pumc-91 and adriamycin-resistant pumc-91/ADM. The expression of DC markers and costimulatory molecules decreased after co-culture. Co-cultured DCs rapidly underwent apoptosis, and had a declined capability to produce IL-8 and RANTES. Furthermore, co-cultured DCs showed impaired allogeneic T cell proliferation and T cell-derived cytokine secretion. Finally, AG490, a Jak2/STAT3 inhibitor, restored the expression of DC markers and costimulatory molecules. Of note, compared with control DCs, DCs co-cultured with pumc-91 produced more IP-10; DCs co-cultured with pumc-91/ADM secreted more MIG. Taken together, these results suggest BCC may inhibit maturation and function of DCs involving of Jak2/STAT3 pathway, and there may be different mechanisms by which adriamycin-resistant BCC restrains DC function in antitumor immune response.
authors.affiliation: Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China.
authors.forename: Weigang
authors.initials: W
authors.lastname: Xiu
authors.affiliation: Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.affiliation: Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lei
authors.affiliation: Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China.
authors.forename: Shangyan
authors.initials: S
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007165:Immunosuppression Therapy; D053614:Janus Kinase 2 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D010641:Phenotype; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000628:therapy*
chemical_list: D018925:Chemokines; D016207:Cytokines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D004317:Doxorubicin; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: anti-tumor immunity; bladder cancer; dendritic cell; immunotherapy; Janus kinase 2/signal transducer and activator of transcription 3 pathway