title: Harnessing the PD-1 pathway in renal cell carcinoma: current evidence and future directions.
abstract: Programmed cell death-1 (PD-1) is a recognized immune checkpoint. It is frequently upregulated on the T cells that infiltrate tumors, providing an inhibitory signal, which may facilitate immune escape. Blocking antibodies have been developed to interrupt the interaction of PD-1 with its ligands PD-L1/PD-L2, with the goal of increasing the host antitumor immune response. Initial results have been encouraging, with durable responses in both treatment-naive and pretreated patients, along with an acceptable toxicity profile. This tolerability makes PD-1 blockade an excellent potential partner for combination strategies with the approved targeted agents, such as tyrosine kinase inhibitors (TKIs) and anti-vascular endothelial growth factor (anti-VEGF) antibodies, as well as other investigational immune checkpoint inhibitors or agonist antibodies that may costimulate an immune response. PD-L1 expression on tumor cells and tumor-infiltrating immune cells is also being evaluated as a predictive biomarker of response to treatment. This review summarizes the biological basis, preclinical studies, ongoing trials, and future challenges associated with targeting the PD-1 pathway in renal cell carcinoma.
authors.affiliation: Department of Internal Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Tripathi
authors.forename: Charles G
authors.initials: CG
authors.lastname: Drake
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Harshman
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D061026:Programmed Cell Death 1 Receptor