title: Aminobisphosphonates and Toll-like receptor ligands: recruiting Vγ9Vδ2 T cells for the treatment of hematologic malignancy.
abstract: Gamma delta (γδ) T cells are intrinsically important for preventing the development and progression of hematologic cancers. These innate T cells are particularly suited for the application of cancer therapy due to the fact they: 1) recognize transformed cells independent of antigen processing or presentation by classical MHC molecules, and 2) embody the anti-tumour effector functions of both NK cells and cytotoxic T cells. It was serendipitously discovered that aminobisphosphonates (ABP), a class of drugs used as adjuvant cancer therapy for the treatment of malignant osteolytic bone disease, have the unexpected side-effect of potently activating the antitumour effector functions of human peripheral γδ T cells. Such beneficial therapeutic synergisms are rare, and no time has been wasted to determine how to best harness the anti-cancer potential of γδ T cells and ABP. Despite promising experimental results, the full clinical potential of this immunotherapeutic strategy has been hampered by the subversive strategies employed by cancer cells to obstruct activation of anti-tumour immune responses. These include the promotion of regulatory T cells (Tregs) that maintain tumour tolerance and the corruption of dendritic cell (DC) function and maturation. Toll-like receptor (TLR) agonists have a long history of breaking free of tumour-induced immune-suppression by resetting DC function and abrogating Treg induced tolerance. This review presents data to support the notion that TLR signalling may perfectly complement the anti-tumour synergy of ABP and activated γδ T cells, and this combined innate artillery could provide the necessary ammunition to topple malignancy's stronghold on the immune system.
authors.affiliation: Institute of Immunology, Christian-Albrechts University Kiel, Arnold-Heller Strasse 3, Haus 17, D-24105 Kiel, Germany. kalyan@immunologie.uni-kiel.de
authors.forename: S
authors.initials: S
authors.lastname: Kalyan
authors.forename: D
authors.initials: D
authors.lastname: Wesch
authors.forename: D
authors.initials: D
authors.lastname: Kabelitz
mesh_terms: D000818:Animals; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008024:Ligands; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D004164:Diphosphonates; D008024:Ligands; D016692:Receptors, Antigen, T-Cell, gamma-delta; C521523:T-cell receptor Vdelta2, human; C521522:T-cell receptor Vgamma9, human; D051193:Toll-Like Receptors