Single-cell RNA-Seq shows that TNFR2 is one of the most markedly increased genes expressed by Tregs, when compared with CD4+ effector T cells (Teffs) cells and CD8+ cytotoxic T lymphocytes (CTLs) in metastatic melanoma patients, and the expression of TNFR2 is associated with CD8+ CTLs exhaustion (33). This evidence concerns the gene CD8A and metastatic melanoma.