Paired sc-RNA and sc-TCR-seq analysis of melanoma patient specimens demonstrated that clonal T cells in periphery are in a more activated cellular state (CCL5+GZMB+KLRG1+KLRK1+CX3CR1+) than their counterparts in TME (PD-1+LAG3+CTLA-4+TIM-3+TIGIT+) (155). This evidence concerns the gene CTLA4 and melanoma.