How can immune checkpoint inhibitors be used to boost immunotherapy?

Immune checkpoint inhibitors are a category of drugs which can regulate immune responses by blocking proteins produced by immune and cancer cells. Immune checkpoint proteins include the interaction of PD-L1 (tumor cell) with PD-1 (T-cell) when a T-cell is bound to a tumor cell.1 Another example includes CTLA-4 in T-cells and B7-1/B7-2 in cancer cells. Immune checkpoint inhibitor proteins prevent T-cells from targeting tumor cells. Checkpoint inhibitors can remove this suppressive effect which allows T-cells to kill tumor cells. Monoclonal antibodies raised against immune checkpoint proteins have been used in clinical trials with robust outcomes in patients that respond well to this form of immunotherapy.2 The efficacy of regulating immune checkpoint proteins is not consistent in all patients as other factors such as their sensitivity to DNA repair and their genomic mutation load can influence response to inhibitors. Predicting better outcomes to checkpoint inhibition requires developing further biomarkers alongside pre-clinical investigations into the regulation of checkpoint proteins by neoantigen abundance, tumor mutation load, DNA repair activity and immune filtration.

1. S.L. Topalian et al, "Immune Checkpoint Blockade: A Common Denominator," Cancer Cell 27(4): 450-461, 2015.
2. S.M. Ansell et al, "PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma," N Engl J Med 372(4): 311-319, 2015.