title: Targeting myeloma-osteoclast interaction with Vγ9Vδ2 T cells.
abstract: Multiple myeloma (MM) cells stimulate osteoclastogenesis, and osteoclasts (OCs) in turn enhance MM growth and drug resistance, resulting in a vicious cycle. Vγ9Vδ2 T cells exert potent anti-tumor effects, making T cell-based immunotherapies using these cells attractive candidates for currently incurable malignancies, such as MM. However, the impact of such treatments on the MM-OC interaction is largely unknown. We demonstrate here that Vγ9Vδ2 T cells expanded by zoledronic acid and IL-2 exerted potent cytotoxic effects on both MM cells and OCs, even in coculture settings, but showed no such effect on bone marrow stromal cells. Vγ9Vδ2 T cells marginally affected colony formation from normal hematopoietic progenitors, and furthermore migrated toward osteopontin and MIP-1α, factors produced by the MM-OC interaction. These results suggest that Vγ9Vδ2 T cells expanded by zoledronic acid and IL-2 are able to migrate to MM bone lesions and preferentially target OCs as well as MM cells, thereby inhibiting both tumor expansion and bone destruction.
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Qu
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.|Division of Internal Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Shibata
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Oda
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Amou
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Nakano
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Yata
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.|Department of Biomaterials and Bioengineering, University of Tokushima Graduate School of Oral Sciences, Tokushima, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiasa
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.|Department of Orthodontics and Dentofacial Orthopedics, University of Tokushima Graduate School of Oral Sciences, Tokushima, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Shingen
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Miki
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Harada
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kagawa
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.|Division of Internal Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ozaki
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan. masabe@clin.med.tokushima-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Abe
mesh_terms: D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D018929:Cell Culture Techniques / Q000379:methods; D002465:Cell Movement / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D004164:Diphosphonates / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid