fig3

Figure 3. General Concept of Developing Drugs Blocking Activity of T_reg cells: In general, there are three main compartments enriched in T_reg cells, which are currently being targeted with drugs: (1) Extracellularly by blocking Ligands (white background), such as IL-2. Alternatively, blocking specific receptors on T_reg cells, e.g., CTLA-4, CCR4, with monoclonal antibodies, such as ipilimumab or mogamulizumab, can arrest the activity of T_reg cells; (2) Intracellularly (red background), signaling pathways can be blocked with small molecule inhibitors, e.g., targeting PI3K-δ; (3) Transcription, gene modification is targeted with different pharmacological agents, such as antisense oligonucleotides, molecular glue, and small molecules. These pharmacological interventions are mainly in non-clinical or early clinical investigations. They target a variety of factors, of which HELIOS and FOXP3 are perhaps the most unique to T_reg cells. T_reg cells: T regulatory cells; IL: interleukin; CTLA-4: cytotoxic T lymphocyte antigen-4; CCR4: C-C chemokine receptor; PI3K-δ: phosphoinositide-3-kinase delta; FOXP3: forkhead box protein P3.