@article {1293159, title = {Inhibitors of the PD-1 Pathway in Tumor Therapy}, journal = {J Immunol}, volume = {200}, number = {2}, year = {2018}, month = {2018 Jan 15}, pages = {375-383}, abstract = { The programmed death 1 (PD-1) pathway delivers inhibitory signals that function as a brake for immune responses. This pathway limits the initiation and duration of immune responses, thereby protecting tissues from immune-mediated damage and autoimmune diseases. However, the PD-1 pathway also inhibits immune responses to tumors. The critical role of PD-1 in preventing antitumor immunity is demonstrated by the transformative effects of PD-1 pathway blockade in a broad range of cancers with the hallmark of durability of response. Despite this success, most patients do not respond to PD-1 monotherapy, and some patients experience adverse events. In this review, we discuss the functions of the PD-1 pathway and its translation to cancer immunotherapy. We also consider current challenges and opportunities for PD-1 cancer immunotherapy, including mechanisms of response and resistance, identification of biomarkers of response to PD-1 therapy, characterization and treatment of PD-1 therapy-related adverse events, and development of safe and effective combination therapies. PubMed\ DOI }, issn = {1550-6606}, doi = {10.4049/jimmunol.1701044}, author = {LaFleur, Martin W and Muroyama, Yuki and Drake, Charles G and Sharpe, Arlene H} }