title: Targeting CD8+ T-cell tolerance for cancer immunotherapy.
abstract: In the final issue of Science in 2013, the American Association of Science recognized progress in the field of cancer immunotherapy as the 'Breakthrough of the Year.' The achievements were actually twofold, owing to the early success of genetically engineered chimeric antigen receptors (CAR) and to the mounting clinical triumphs achieved with checkpoint blockade antibodies. While fundamentally very different, the common thread of these independent strategies is the ability to prevent or overcome mechanisms of CD8(+) T-cell tolerance for improved tumor immunity. Here we discuss how circumventing T-cell tolerance has provided experimental insights that have guided the field of clinical cancer immunotherapy to a place where real breakthroughs can finally be claimed.
authors.affiliation: Saint Louis University School of Medicine, Department of Molecular Microbiology & Immunology, 1100 South Grand Blvd, St Louis, MO 63104, USA.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Jackson
authors.forename: Jinyun
authors.initials: J
authors.lastname: Yuan
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Teague
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005818:Genetic Engineering; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007167:Immunotherapy / Q000379:methods*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology
chemical_list: D011948:Receptors, Antigen, T-Cell
keywords: CD8+ T-cell checkpoint blockade; adoptive cell transfer; cancer immunotherapy; cancer vaccine; chimeric antigen receptor; lymphodepletion; tolerance