The article discusses the role of regulatory T (Treg) cells in cancer immunotherapy. Treg cells, which express the transcription factor FOXP3, are known to suppress both self-antigen and tumor antigen-specific immune responses. Their infiltration into tumor tissues is often associated with poor prognosis. However, removing Treg cells can evoke and enhance anti-tumor immune responses. The authors highlight the need to specifically target effector Treg cells rather than all FOXP3+ T cells to avoid autoimmunity. They explore various strategies, including the use of cell surface molecules like CCR4 and CTLA-4, to selectively deplete effector Treg cells. Additionally, they discuss the potential of combining Treg-cell targeting with the activation of tumor-specific effector T cells, such as through cancer vaccines or immune checkpoint blockade, to improve the effectiveness of cancer immunotherapy. The article emphasizes the importance of understanding the functional heterogeneity of FOXP3+ T cells and the sequence of treatments to maximize the benefits of Treg-cell targeting while minimizing autoimmunity.The article discusses the role of regulatory T (Treg) cells in cancer immunotherapy. Treg cells, which express the transcription factor FOXP3, are known to suppress both self-antigen and tumor antigen-specific immune responses. Their infiltration into tumor tissues is often associated with poor prognosis. However, removing Treg cells can evoke and enhance anti-tumor immune responses. The authors highlight the need to specifically target effector Treg cells rather than all FOXP3+ T cells to avoid autoimmunity. They explore various strategies, including the use of cell surface molecules like CCR4 and CTLA-4, to selectively deplete effector Treg cells. Additionally, they discuss the potential of combining Treg-cell targeting with the activation of tumor-specific effector T cells, such as through cancer vaccines or immune checkpoint blockade, to improve the effectiveness of cancer immunotherapy. The article emphasizes the importance of understanding the functional heterogeneity of FOXP3+ T cells and the sequence of treatments to maximize the benefits of Treg-cell targeting while minimizing autoimmunity.