Sam Santhosh, Hiranjith G.H., Michael Nemzek and Amitabha Chaudhuri
Currently approved checkpoint inhibitors are antibodies that block the function of three key proteins expressed on the surface of T cells: CTLA-4, PD-1 and PD-L1.
Under normal conditions, these proteins function as brakes to prevent immune-related toxicity from arising because of persistent T cell activity. Cancer hijacks this essential function of immune homeostasis to protect itself from immune-mediated elimination [1, 2]. By expressing high levels of PD-L1, tumor cells engage PD-1 receptors on T cells, suppressing their anti-tumor activity and escaping T cell-mediated killing. By blocking PD-1 and PD-L1 signaling, the checkpoint inhibitors remove the brakes on T cells imposed by the tumor and enhance their anti-tumor activity .