title: Programmed cell death 1-directed immunotherapy for enhancing T-cell function.
abstract: T-cell exhaustion is a unique state that appears during many chronic infections and cancer and is characterized by loss of proliferative capacity and effector function. Complex mechanisms are involved in this T-cell dysfunction but an inhibitory receptor, PD-1, has been identified as a major regulator of T-cell exhaustion. Blockade of the PD-1 pathway can reinvigorate exhausted T cells, resulting in better control of chronic infections and cancer. Notably, recent clinical studies have revealed that PD-1-directed immunotherapy is highly effective in cancer patients, demonstrating that PD-1 is a promising therapeutic target in humans. In this review, we summarize our current understanding of the epigenetic regulation of PD-1 expression in T cells and discuss potential combination therapy with PD-1 blockade toward developing more effective treatment for chronic infections and cancer.
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322.
authors.forename: Koichi
authors.initials: K
authors.lastname: Araki
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322.
authors.forename: Ben
authors.initials: B
authors.lastname: Youngblood
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322 rahmed@emory.edu.
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D016923:Cell Death; D016207:Cytokines / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007239:Infections / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
chemical_list: D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D061026:Programmed Cell Death 1 Receptor