The antimetabolite pemetrexed induced PD-L1 upregulation by activating the ROS-NF-κB signaling pathway through inactivation of thymidylate synthase and thus in combination with PD-1 monoclonal antibody activation of CD4+ T cells and CD8+ T cells provides a more favorable immune microenvironment for tumor growth inhibition (46) (Table 1, Figure 3). Here, CD4 is linked to neoplasm.