Thus, therapies targeting checkpoint inhibitory pathways such as the PD-L1/PD-1 signaling axis have emerged as a gold-standard cancer immunotherapy treatment of choice.30,54 Recently, anti-PD-1 therapy with the clinically used monoclonal antibody nivolumab was demonstrated to reduce bone cancer pain and osteoclast formation in a murine model of bone cancer.89 In addition, mice lacking PD-1 exhibited reduced bone cancer pain after intrafemoral inoculation with LLC cells. Here, PDCD1 is linked to cancer.