For the first time, the present study characterizes by using cutting-edge digital spatial proteomic and genome-wide transcriptomic lung profiling combined with conventional immunofluorescence, the expression of the immune checkpoint PD-L1 in structural and inflammatory cells from two independent cohorts of COPD and lung cancer (NSCLC) patients and never- and ever-smoker controls. Here, CD274 is linked to chronic obstructive pulmonary disease.