Figure 2

T cell activation. B7-CD28 co-stimulation pathway is needed for T cell activation and CTLA4 Ig blocks this pathway leading to T cell inactivation. Lenalidomide acts by directly inducing tyrosine phosphorylation of CD28 on T cells leading to activation of downstream targets such as PI3K, GRB-2-OS, and NF-κb, thus partially overcoming CTLA4 Ig blockade and leading to T cell clonal proliferation.