The benefit of the combined effect of anti-RL and immune-checkpoint inhibitors will be investigated in the CHARLI trial (NCT03161756), a phase I/II study of the effect of denosumab in combination with nivolumab (an anti-PD-1), with or without ipilimumab (anti-CTLA4), in metastatic melanoma patients, and in the POPCORN trial (ACTRN12618001121257), which will evaluate immune changes in NSCLC patients treated with nivolumab alone or in combination with denosumab. The gene discussed is RELN; the disease is metastatic melanoma.