Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti–CTLA-4 antibodies

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical negative regulator of immune responses. Uniquely among known inhibitory receptors, its genetic ablation results in a fulminating and fatal lymphoproliferative disorder. This central regulatory role led to the development of antibodies designed to block CTLA-4 activity in vivo, aiming to enhance immune responses against cancer. Despite their preclinical efficacy and promising clinical activity against late stage metastatic melanoma, the critical cellular targets for their activity remains unclear. In particular, debate has focused on whether the effector T cell (T(eff)) or regulatory T cell (T reg cell) compartment is the primary target of…

• HH
  Howard Hughes Medical Institute
• CR
  Cancer Research Institute
• BS
  Bristol-Myers Squibb
• MS
  Memorial Sloan-Kettering Cancer Center
• UC
  University College London