TLR9 Agonists Potentiate Adoptive T-cell Therapy in Cancer through a B-cell-CD2 Costimulatory Axis.

TLR9 agonists enhance adoptive T cell therapy by activating a B cell-CD2 costimulatory pathway, leading to improved tumor control and T cell function.

• Why it matters: Understanding how TLR agonists boost T cell therapy can help optimize cancer treatments and overcome resistance in solid tumors, addressing a critical gap in immunotherapy.
• What they did: The study used both murine and human models to show that TLR9-activated B cells promote CD8+ T cell fitness via CD2-dependent costimulation, with class B CpG uniquely enhancing effector differentiation and metabolic capacity.
• The result: Blocking CD2 reduced the benefits of TLR9 agonists, while CD2 stimulation mimicked these effects, and higher CD2 expression in human tumors correlated with better survival, highlighting a targetable pathway for improving ACT outcomes.