title: Dendritic cells loaded with myeloma cells pretreated with a combination of JSI-124 and bortezomib generate potent myeloma-specific cytotoxic T lymphocytes in vitro.
abstract: Signal transducer and activator of transcription 3 (STAT3) is highly activated in multiple myeloma. Activated STAT3 promotes survival and proliferation of cancer cells, suppresses Th1 immune response, and induces dysfunction of immune cells. We investigated whether pretreating myeloma cells with a phosphor (p)-STAT3 inhibitor (JSI-124) and/or bortezomib before loading into dendritic cells (DCs) can affect DC function. The combination treatment with JSI-124 and bortezomib resulted in the highest expression of heat shock protein (HSP) 90 and the lowest expression of p-STAT3 in dying myeloma cells. DCs loaded with dying myeloma cells treated by JSI-124 and bortezomib produced the least amount of p-STAT3 compared to other treatments. The DCs were recovered from abnormal cytokine secretions of interleukin (IL)-10, IL-6, and IL-23 without any effect on production of IL-12p70. DCs loaded with JSI-124 and bortezomib treated, dying myeloma cells most potently generated myeloma-specific cytotoxic T lymphocytes (CTLs). The data suggest that pretreatment of myeloma cells with JSI-124 and bortezomib can recover DC function through the up-regulation of HSP90 and the down-regulation of p-STAT3 and inhibitory cytokines, and that these DCs can potently generate myeloma-specific CTLs.
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea; Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Vaxcell-Bio Therapeutics, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Youn-Kyung
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea; The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Nu-Ri
authors.initials: NR
authors.lastname: Choi
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea; The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Manh-Cuong
authors.initials: MC
authors.lastname: Vo
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea; The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Republic of Korea.
authors.forename: My-Dung
authors.initials: MD
authors.lastname: Hoang
authors.affiliation: Vaxcell-Bio Therapeutics, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Mi-Seon
authors.initials: MS
authors.lastname: Lim
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea; Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Thanh-Nhan
authors.initials: TN
authors.lastname: Nguyen-Pham
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea; Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea; Vaxcell-Bio Therapeutics, Hwasun, Jeollanamdo, Republic of Korea; The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Republic of Korea. Electronic address: drjejung@chonnam.ac.kr.
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011719:Pyrazines / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000276:immunology; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D016207:Cytokines; D011719:Pyrazines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014315:Triterpenes; D000069286:Bortezomib; C038106:cucurbitacin I