The process of immune regulation involves several pathways related to T-cell and B-cell activation, proliferation, foreign antigen elimination, and induction of tumor cell death. Cytotoxic T-lymphocyte associated protein 4 (CTLA4) is a cell-surface receptor expressed on CD4+ and CD8+ T-cells, and programmed cell death 1 (PD-1) is a cell surface receptor expressed on T-cells and pro-B-cells. Both are components of the immune checkpoint that functions in blocking the activation of a T-cell response. 
Figure 1. CTLA4 receptor stimulation negatively regulates the immune system by switching off the T-cell response, preventing the further activation of the adaptive immune response by inhibiting AKT. PD-1 receptor stimulation (PD-L1 and PD-L2 expressed on Antigen-Presenting cells) negatively regulates the immune system by switching off the T-cell responseópreventing further activation of the adaptive immune response. Specific nodes in the pathway that are therapeutically actionable are noted.
Biomarkers in the immune checkpoints pathway serve as inclusion eligibility criteria in 27 clinical trials, of which 22 are open and 5 are closed. The genes IL7R, BTK, MYD88, IRF4, and MPL on this pathway most frequently harbor alterations that are inclusion eligibility criteria for clinical trials.
Of the trials that contain alteration(s) in the immune checkpoints pathway as inclusion criteria, 9 are phase 1 (6 open), 4 are phase 1/phase 2 (3 open), 12 are phase 2 (11 open), 1 is phase 2/phase 3 (1 open), and 1 is phase 3 (1 open) .