CD4 and neoplasm: Thus, (1) PD-L1 and PD-L2 expressing tumor cells, (2) PD-L1 and PD-L2 expressing infiltrating T-cells of the TME, (3) PD-L1 expressing CAFs of the TME, and (4) PD-L1 and PD-L2 expressing macrophages of the TME can initiate PD-L1/L2-mediated immune checkpoint inhibition by binding with PD-1 receptors expressed on CD3+/CD4+/CD8+ T-lymphocytes in the TME.