Previous studies have revealed that higher Treg abundance was associated with shorter overall survival in renal cancer, breast cancer or melanoma (50), while high infiltration of Foxp3+ Treg cells in HNSCC was associated with an improved overall survival (51), and studies have revealed that higher CD8+ T cell or NK cell infiltration was usually accompanied by higher infiltration of Tregs in HNSCC (51); therefore it is hypothesized that Tregs are trafficked into the TME after CD8+ T and NK cells as a negative feedback to prevent the excessive inflammation mediated by CD8+ T cells and NK cells. The gene discussed is CD8A; the disease is melanoma.