Unlocking the Role of Treg Cells Immune Response and Infectious Risk Following CAR T-Cell Therapy in Patients with Cancer

Chimeric antigen receptor (CAR) T-cell therapy has brought hope for patients with cancer and showed promising results and a high cure rate in various types of hematological malignancies. However, cellular therapy can lead to profound immunodeficiency of the innate and adaptive immune systems, whether at the systemic or at the local cellular immune response, which is a major predisposing risk factor for invasive opportunistic infection, including fungal, viral, and bacterial pathogens. The role of regulatory T-cells (Tregs) and their antigen specificity in humans remains largely unknown, but Tregs have been implicated in a wide range of modulating viral and fungal infections. Though there have been many advancements regarding the use of CAR T-cells in treating hematological malignancies, the intricate and homeostatic role of Tregs in influencing therapeutic outcomes and infection risk remains underexplored. Most published literature on this topic focuses on the role of Treg in the immunosuppression necessary for successful CAR T-cell therapy rather than the dual function of Treg in immunosuppression and immune recovery. We intend to bridge this gap with a specific focus on the contribution of Tregs in the modulation of CAR T-cell efficacy and their role in opportunistic infections after therapy. In this review, we described the potential role and dynamics of Tregs following CAR T-cell therapy, offering an expanded understanding of their impact on patient outcomes and highlighting areas for future research.