CD28 and neoplasm: Seminal work in the 1990s revealed the antagonistic roles of CD28 and CTLA-4 in T cell activation: CD28 co-stimulation blockade suppressed T cell priming (50–60 % reduction in IL-2 secretion), whereas CTLA-4 inhibition amplified effector responses (2.3-fold increase in tumor-infiltrating lymphocytes) [129].