CD137-expressing regulatory T cells in cancer and autoimmune diseases

Regulatory T cells (Tregs) are essential for maintaining immune homeostasis, with critical roles in preventing aberrant immune responses that occur in autoimmune diseases and chronic inflammation. Conversely, the abundance of Tregs in cancer is associated with impaired anti-tumor immunity, and tumor immune evasion. Recent work demonstrates that CD137, a well-known costimulatory molecule for T cells, is highly expressed on Tregs in pathological conditions, while its expression is minimal or negligible on peripheral Tregs. The expression of CD137 marks Tregs with potent immunosuppressive phenotype that foster cancer progression and are protective against certain autoimmune diseases. Hence CD137 has emerged as a marker for Tregs. However, several important questions still remain regarding the expression and function of CD137 in Tregs. Here, we provide an overview of our current knowledge of Treg mechanisms of action, with a focus on the role of CD137 in modulating Treg activity. We also explore the implications of CD137⁺ Tregs in both cancer and autoimmune diseases, emphasizing the significance of targeting these cells for therapeutic intervention in these conditions.