title: [Regulation of T-cell immune exhaustion and cancer immunotherapy].
abstract: In chronic infectious diseases and cancer, CD8⁺ T cells specific for viral and/or tumor antigens undergo repeated T cell receptor (TCR) stimulation due to the persistence of pathogens or cancer cells, gradually losing their ability to secrete interleukin 2 (IL-2), tumor necrosis factor-a (TNF-a), and interferon-g (IFN-g). These CD8⁺ T cells are finally eliminated by apoptosis, a process referred to as immune exhaustion. The worsening immune function is accompanied by phenotypic changes in CD8⁺ T cells, for example, by changes in the expression of exhaustion markers such as programmed cell death protein 1(PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), T cell immunoglobulin mucin 3 (TIM-3), and lymphocyte activation gene 3 (LAG-3). The exhaustion molecules on CD8⁺ T cells interact with their respective ligands and induce negative signals in activated T cells, leading to CD8⁺ T cell dysfunction. In 2013, the combined use of anti-PD-1 and anti- CTLA-4 antibodies was shown to induce extraordinary anti-tumor effects in patients with advanced melanoma. The regulation of exhausted CD8⁺ T cells has now emerged as a promising therapy to treat cancer.
authors.affiliation: Dept. of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.
authors.forename: Shingo
authors.initials: S
authors.lastname: Eikawa
authors.forename: Heiichiro
authors.initials: H
authors.lastname: Udono
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D018450:Disease Progression; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D013312:Stress, Physiological; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines