Releasing the Brake on the Immune System: The PD-1 Strategy for Hematologic Malignancies

Manipulation of the immune system as a viable cancer treatment strategy has re-emerged. The programmed death 1 (PD-1) pathway is an important, physiologic immune checkpoint necessary to limit autoimmune processes but co-opted by tumors to suppress the antitumor response and allow tumor escape. Blockade of the PD-1 pathway through the use of PD-1 or PD ligand 1(PD-L1) antibodies releases this brake on the immune response. The anti-PD-1 antibodies have produced encouraging results across a broad range of malignancies. Many hematologic malignancies have usurped the PD-1 pathway. Recent investigations have explored the use of anti-PD-1 therapy in hematologic malignancies, with encouraging results. Incorporation of PD-1 blockade into the treatment algorithms for hematologic malignancies is currently being pursued in multiple active clinical trials. Here we review the data on anti-PD-1 monoclonal antibodies to date and discuss ongoing and future clinical trials.