Targeting TNFR2 for cancer immunotherapy: recent advances and future directions

Abstract Cancer is the leading cause of death worldwide, accounting for nearly 10 million deaths every year. Immune checkpoint blockade approaches have changed the therapeutic landscape for many tumor types. However, current immune checkpoint inhibitors PD-1 or CTLA-4 are far from satisfactory, due to high immune-related adverse event incident (up to 60%) and the inefficiency in cases of “cold” tumor microenvironment. TNFR2, a novel hopeful tumor immune target, was initially proposed in 2017. It not only promotes tumor cell proliferation, but also correlates with the suppressive function of Treg cells, implicating in the development of an immunosuppressive tumor microenvironment. In preclinical studies, TNFR2 antibody therapy has demonstrated efficacy alone or a potential synergistic effect when combined with classical PD-1/ CTLA-4 antibodies. The focus of this review is on the characteristics, functions, and recent advancements in TNFR2 therapy, providing a new direction for the next generation of anti-tumor alternative therapy.