title: Low-dose bortezomib increases the expression of NKG2D and DNAM-1 ligands and enhances induced NK and γδ T cell-mediated lysis in multiple myeloma.
abstract: Multiple myeloma (MM) is an incurable hematological malignancy, although bortezomib has markedly improved its outcomes. Growing clinical evidence indicates that enhancing induced natural killer (NK) or γδ T cells for infusion is useful in the treatment of MM. However, whether combination treatment with bortezomib and induced NK and γδ T cells further improves outcomes in MM, and how the treatments should be combined, remain unclear. Herein, we found that low-dose bortezomib did not suppress the viability of induced NK and γδ T cells, but did induce MM cell apoptosis. Importantly, low-dose bortezomib increased the expression of NKG2D and DNAM-1 ligands on MM cells, which sensitized the multiple myeloma cells to lysis by induced NK and γδ T cells. Our results suggested that combination treatment with low-dose bortezomib and induced NK or γδ T cells had a synergistic cytotoxic effect on MM cells. This study provided a proof of principle for the design of future trials and investigation of this combination therapeutic strategy for MM treatment.
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Niu
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Haofan
authors.initials: H
authors.lastname: Jin
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.|College of Pharmacy, Jilin University, Changchun 130021, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Jilin University, Changchun 130021, China.
authors.forename: Yulai
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Xu
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Jianting
authors.initials: J
authors.lastname: Xu
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Lianjing
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.|Department of Hematology, Taian Central Hospital, Taian 271000, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Hao
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Jiuwei
authors.initials: J
authors.lastname: Cui
mesh_terms: D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000069286:Bortezomib / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000075942:Intraepithelial Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation; D007694:Killer Cells, Natural / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism* / Q000628:therapy; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D015854:Up-Regulation; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000970:Antineoplastic Agents; D000098862:T Lineage-Specific Activation Antigen 1; C527085:KLRK1 protein, human; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D000069286:Bortezomib
keywords: bortezomib; gamma-delta T cells; multiple myeloma; natural killer cells