The application of different single-cell technologies to three different cohorts of melanoma patients treated with anti-PD-1 allowed to understand that a noteworthy phenotypic heterogeneity is observed within CD8+ TILs that display characteristics of dysfunction, reflected by various combinations and expression levels of inhibitory receptor and activation markers, the proliferative capacity and the ability to produce cytokines and effector molecules. Here, CD8A is linked to melanoma.