In melanoma, the lymphocytic infiltrate is a prognostic parameter classified in "brisk", "non-brisk" and "absent". The meaning of "brisk" is "active", "energetic", implying a functional connotation starting from a morphological evaluation. Surprisingly, this functional connotation has never been proved. Recently, it has been shown that not all brisk infiltrates have a good prognosis, that lymphocytic populations can be very heterogeneous, and that anti-PD-1 immunotherapy supports activated T

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... ls. This urged a thoughtful investigation of the TILs. Here we characterize the immune landscape in primary melanoma through a multiplex panel of 40 immune markers on one single tissue section at single cell resolution, RT-PCR and shotgun proteomics. This approach allowed us a) to categorize the brisk and non-brisk patterns into three functional categories (active, transitional and exhausted); b) to correlate T-cell activation and spontaneous melanoma regression; c) to investigate the most important actors involved in TILs exhaustion.