title: Overcoming T cell exhaustion in infection and cancer.
abstract: Inhibitors of the Programmed Cell Death 1: Programmed Cell Death 1 ligand 1 (PD-1:PD-L1) pathway, a central regulator of T cell exhaustion, have been recently shown to be effective for treatment of different cancers. However, clinical responses are mixed, highlighting the need to better understand the mechanisms of action of PD-1:PD-L1, the role of this pathway in immunity to different tumors, and the molecular and cellular effects of PD-1 blockade. Here, we review the molecular regulation of T cell exhaustion, placing recent findings on PD-1 blockade therapies in cancer in the context of the broader understanding of the roles of the PD-1:PD-L1 pathway in T cell exhaustion during chronic infection. We discuss the current understanding of the mechanisms involved in reversing T cell exhaustion, and outline critical areas of focus for future research, both basic and clinical.
authors: Institute for Immunology and Department of Microbiology, University of Pennsylvania Perelman School of Medicine, 421 Curie Blvd, Philadelphia, PA 19104, USA.
authors: Kristen E
authors: KE
authors: Pauken
authors: Institute for Immunology and Department of Microbiology, University of Pennsylvania Perelman School of Medicine, 421 Curie Blvd, Philadelphia, PA 19104, USA. Electronic address: wherry@mail.med.upenn.edu.
authors: E John
authors: EJ
authors: Wherry
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology*; D002908:Chronic Disease; D006505:Hepatitis / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: PD-1; PD-L1; T cell exhaustion; cancer; chronic infection; immunotherapy