Therapeutic potential of TNFR2 agonists: a mechanistic perspective

TNFR2 agonists have been investigated as potential therapies for inflammatory diseases due to their ability to activate and expand immunosuppressive CD4+Foxp3+ Treg cells and myeloid-derived suppressor cells (MDSCs). Despite TNFR2 being predominantly expressed in Treg cells at high levels, activated effector T cells also exhibit a certain degree of TNFR2 expression. Consequently, the role of TNFR2 signaling in coordinating immune or inflammatory responses under different pathological conditions is complex. In this review article, we analyze possible factors that may determine the therapeutic outcomes of TNFR2 agonism, including the levels of TNFR2 expression on different cell types, the biological properties of TNFR2 agonists, and disease status. Based on recent progress in the understanding of TNFR2 biology and the study of TNFR2 agonistic agents, we discuss the future direction of developing TNFR2 agonists as a therapeutic agents.

Automated summary

TNFR2 agonists have potential as therapies for inflammatory diseases by activating and expanding immunosuppressive Treg cells and MDSCs. However, the role of TNFR2 signaling in immune or inflammatory responses is complex due to its expression on both Treg cells and activated effector T cells. This review analyzes factors that may influence the therapeutic outcomes of TNFR2 agonism and discusses the future direction of developing TNFR2 agonists as therapeutic agents based on recent progress in TNFR2 biology and agonistic agents.