EVs are involved in the cross-talk within the tumor microenvironment and play a role in the inhibition of the anti-tumor immune response and metastasis, in particular by PD-L1 presentation [12–15] So far, only few studies have evaluated the potential of PD-L1 expression in EVs as a predicting biomarker in patients with lung cancer undergoing ICIs and they showed conflicting results that warrant further investigation [16, 17]. This evidence concerns the gene CD274 and lung cancer.