The present study aims to: (i) explore the role of sPD-L1, sB7-H3 and sB7-H4 as prognostic markers in patients with advanced NSCLC treated with nivolumab or pembrolizumab; (ii) assess the involvement of EVs expressing PD-L1, B7-H3 and B7-H4 in the mechanisms of the response to ICIs (Figure 1). This evidence concerns the gene SPDL1 and non-small cell lung carcinoma.