Targeting TNFR2 in Cancer: All Roads Lead to Rome

TNF receptor 2 (TNFR2) has become one of the best potential immune checkpoints that might be targeted, mainly because of its vital role in tumor microenvironments (TMEs). Overexpression of TNFR2 in some tumor cells and essential function in immunosuppressive cells, especially regulatory T cells (Tregs), makes blocking TNFR2 an excellent strategy in cancer treatment; however, there is evidence showing that activating TNFR2 can also inhibit tumor progression in vivo. In this review, we will discuss drugs that block and activate TNFR2 under clinical trials or preclinical developments up till now. Meanwhile, we summarize and explore the possible mechanisms related to them.