For instance, activation of PI3K and deactivation of PTEN results in recruitment and activation of downstream signaling molecules like AKT, enhancing T-cell survival, proliferation and effector functions.6 Under normal conditions, ligation of the inhibitory receptors CTLA-4 and PD-1 results in recruitment of SHP2 phosphatases that dampens TCR signaling as well as CD28 signaling.7–9 As such, kinase activity may reflect anti-tumor T-cell activity and consequently could act as a predictor for clinical outcome after ICI therapy. The gene discussed is CD28; the disease is neoplasm.