Title: Aminobisphosphonates and Toll-Like Receptor Ligands: Recruiting Vγ9Vδ2 T Cells for the Treatment of Hematologic Malignancy
Volume: 18
Issue: 34
Author(s): S. Kalyan, D. Wesch and D. Kabelitz
Affiliation:
Keywords:
Gamma delta T cells, aminobisphosphonates, Toll-like receptor ligands, lymphoma, myeloma, hematologic cancer, immunotherapy, regulatory T cells, (TLR) agonists, malignancy's
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.
