The data shown so far evidence a strong correlation between higher levels of PD-L1+ EVs and the lack of response to ICI when these are released from melanoma cells and CD8+ T cells, further supporting Chen’s hypothesis that exhausted T cells, releasing higher amount of PD-L1+ EVs, can no longer be reinvigorated by anti-PD1 treatment [24]. This evidence concerns the gene CD8A and melanoma.