CD4 and neoplasm: For example, low dose of cyclophosphamide can inhibit and deplete regulatory T cells and enhance the anti-tumor activities of CD4 T, CD8 T, natural killer (NK), or dendritic cells (27–29); 5-Fluorouracil and other p53-activating cytotoxic drugs can upregulate the expression and release of tumor-associated immunogen and enhance the antigen presentation function of dendritic cells (30, 31); antiangiogenic agents can improve the response of immunotherapy by targeting VEGF or VEGFR because VEGF can enhance expression of PD-1 and other inhibition checkpoints involved in CD8 T-cell exhaustion (32).