CD28 costimulation is organized by signaling condensates and counteracted by PD-1.

CD28 co-stimulation is organized by signaling condensates involving Lck, and PD-1 counteracts this process through phosphorylation-dependent dissolution.

• Why it matters: Understanding how T cell activation signals are physically organized is crucial for improving immunotherapies, yet the mechanisms of signal compartmentalization remain unclear.
• What they did: The study used a reconstituted system to show that CD28 ICD forms condensates with Lck, PI3K, and GRB2, and identified PD-1 as a regulator that dissolves these condensates depending on its phosphorylation state.
• The result: Engineered CD28 mutants resistant to PD-1 disruption enhanced CAR T cell efficacy in vivo, suggesting that manipulating condensation mechanisms can improve therapeutic T cell resilience.