Immune regulatory checkpoints, such as PD-1/PD-L1 or OX-40/OX-40L, and soluble leverage factors, such as vascular endothelial growth factor (VEGF), IL-6, TGF-β, or TNF-a perform crucial roles in these immunosuppressive networks thus causing unsatisfactory clinical responses in immunotherapy of advanced cancer. Here, TNFRSF4 is linked to cancer.