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 gamma delta T 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 gamma delta T cells. In addition, we discuss the emerging clinical evidence that N-BPs have a role in cancer immunotherapy.