Nitrogen-containing bisphosphonates and cancer immunotherapy.
Bisphosphonates, especially nitrogen-containing bisphosphonates (N-BPs), are widely used to block bone destruction in cancer patients with bone metastasis because they are effective inhibitors of osteoclast-mediated bone resorption. In addition to their antiresorptive effects, preclinical evidence strongly suggests that N-BPs have anticancer activity. Some of the activities associated with N-BPs are observed in human γδT cells that straddle the interface of innate and adaptive immunity and have potent anti-tumour activity. This review examines the molecular and cellular mechanisms through which N-BPs stimulate the expansion and cytotoxic activity of human γδ T cells. In addition, we discuss the emerging clinical evidence that N-BPs have a role in cancer immunotherapy.
Clézardin
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INSERM, Research Unit U664, University of Lyon-1, Faculty of Medicine Laennec, rue Guillaume Paradin, 69372 Lyon cedex 08, France. philippe.clezardin@inserm.fr
Massaia
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D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000556:secondary; D001862:Bone Resorption / Q000188:drug therapy / Q000517:prevention & control; D004164:Diphosphonates / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation / Q000187:drug effects*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009584:Nitrogen / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D009584:Nitrogen