CD4+CD25+ FOXP3+ regulatory T (Treg) cells, Ly6G+ neutrophils, MDSCs, and macrophages help build an immunosuppressive pre-metastatic niche, whereas TH1 CD4+ or CD8+ T cells, Ly6G- neutrophils, and NK cells have the opposite functions.67 NK cells are downregulated in primary lung adenocarcinomas and lung cancer metastases compared with those in normal lung tissues.68,69 Fischer et al.70 compared the molecular profile of 88 melanoma brain metastases (MBMs) and 42 matched extracranial metastases with RNA sequencing (RNA-seq) data. This evidence concerns the gene CD8A and melanoma.