As new studies make evident that distinct metastatic sites– e.g. lung versus liver - and mutational profiles mechanistically implicated in aneuploidy (26, 27, 29) – BRAF V600E versus V600K, as well as 9p21 loss, where CDKN2A/B reside - are associated with differences in ICI treatment response in melanoma (99, 119, 120), future efforts on the understanding of the tumor-immune interaction need to account for organ-specific immune cell composition and mutational background of the tumors at high resolution, as evidenced by a recent study based on single-cell sequencing in uveal melanoma (121). This evidence concerns the gene BRAF and uveal melanoma.