CD4 and neoplasm: In addition, both characterization of the tumor immune infiltrate by CD8+ and regulatory CD4+ T cells and detection of tumor immune escape mechanisms, including programmed death-ligand 1 (PD-L1) up-regulation and human leukocyte antigen (HLA) class I down-regulation on cancer and/or immune cells, have been shown to better define the melanoma disease course (17–23).