Our study together with the previous ones [7, 8] allowed a breakthrough in the characterization of the role of circulating PD1 and PD-L1, having shown that only a part of them, i.e. three subpopulations of circulating EVs positive for the two checkpoints and released from melanoma cells, T cells and DCs, was actively involved in the prediction of response/resistance to anti-PD1 and closely related to the innate anti-PD1 resistance [8]. The gene discussed is PDCD1; the disease is melanoma.