Targeting myeloma–osteoclast interaction with Vγ9Vδ2 T cells

• Published in: International journal of hematology Vol. 94; no. 1; pp. 63 - 70
• Main Authors: Cui, Qu, Shibata, Hironobu, Oda, Asuka, Amou, Hiroe, Nakano, Ayako, Yata, Kenichiro, Hiasa, Masahiro, Watanabe, Keiichiro, Nakamura, Shingen, Miki, Hirokazu, Harada, Takeshi, Fujii, Shiro, Kagawa, Kumiko, Takeuchi, Kyoko, Ozaki, Shuji, Matsumoto, Toshio, Abe, Masahiro
• Format: Journal Article
• Language: English
• Published: Japan Springer Japan 01.07.2011; Springer
• Subjects: Biological and medical sciences; Cell Communication - drug effects; Cell Communication - immunology; Cell Culture Techniques - methods; Cell Movement - drug effects; Cytotoxicity, Immunologic; Diphosphonates - pharmacology; Hematologic and hematopoietic diseases; Hematology; Humans; Imidazoles - pharmacology; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Interleukin-2 - pharmacology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Medicine; Medicine & Public Health; Multiple Myeloma - immunology; Multiple Myeloma - pathology; Multiple Myeloma - therapy; Oncology; Original Article; Osteoclasts - drug effects; Osteoclasts - pathology; Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Zoledronic acid; Osteoclast; Immunotherapy; Vγ9Vδ2 T cell; Multiple myeloma; Antineoplastic agent; Immunopathology; Targeting; Hematology; γ/δ T cell receptor; Antiresorptive agent; Diphosphonic acid derivatives; B cell neoplasm; Malignant hemopathy; Lymphoid neoplasm; Myeloma; Bisphosphonates; Osteoarticular system; Treatment; Immunoglobulinopathy; Lymphoproliferative syndrome; T-Lymphocyte; Bone; Cancer
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-011-0885-9

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.