By comparing the communication signals between CTL and CTL_ex with tumor cells (Figure 7C, Figures S10A,B and S11B–D; Table S4E), we identified the following key signals affecting T cell cytotoxicity in different melanoma ecosystems: IFNG–(IFNGR1 + IFNGR2), MIF–(CD74 + CXCR4), APP–CD74, HLA–E–CD94, HLA–E–CD94 in CM; CD99–CD99, HLA–E–KLRC1, HLA–E–CD94, ADGRE5–CD55 in AM; and MIF–CD74, APP–CD74, SIRPG–CD47 in UM. This evidence concerns the gene CXCR4 and melanoma.