[The roles of TNFR2 signaling in tumors and advances in TNFR2 immunotherapy].

Abstract

Tumor necrosis factor receptor 2 (TNFR2) is a type I transmembrane glycoprotein receptor expressed in various tumor cells and certain immune cells, particularly regulatory T cells. TNFR2 coordinates multiple signaling pathways to promote tumor initiation and growth, activate immunosuppressive cells, modulate the tumor microenvironment, and facilitate immune escape and tumor progression. In recent years, immunotherapy has been incorporated into the treatment of malignant tumors, yet monotherapy with immune checkpoint inhibitors often suffers from low response rates and frequent immune related adverse events. To further improve therapeutic efficacy, combination immunotherapies have attracted increasing attention. Numerous studies have demonstrated that TNFR2 antibodies exhibit synergistic effects when combined with classical immune checkpoint inhibitors such as programmed death 1 (PD-1)/cytotoxic T lymphocyte associated protein 4 (CTLA-4) antibodies. Clarifying the role and mechanism of TNFR2 in tumor development is crucial for designing effective combination treatment strategies. This article reviews the expression, function, and mechanisms of TNFR2 in tumors, analyzes the opportunities and challenges in its targeted therapy, and provides new insights and perspectives for clinical oncology.