title: Negative immune checkpoints on T lymphocytes and their relevance to cancer immunotherapy.
abstract: The term 'inhibitory checkpoint' refers to the broad spectrum of co-receptors expressed by T cells that negatively regulate T cell activation thus playing a crucial role in maintaining peripheral self-tolerance. Co-inhibitory receptor ligands are highly expressed by a variety of malignancies allowing evasion of anti-tumour immunity. Recent studies demonstrate that manipulation of these co-inhibitory pathways can remove the immunological brakes that impede endogenous immune responses against tumours. Antibodies that block the interactions between co-inhibitory receptors and their ligands have delivered very promising clinical responses, as has been shown by recent successful trials targeting the CTLA-4 and PD-1 pathways. In this review, we discuss the mechanisms of action and expression pattern of co-inhibitory receptors on different T cells subsets, emphasising differences between CD4(+) and CD8(+) T cells. We also summarise recent clinical findings utilising immune checkpoint blockade.
authors.affiliation: Cancer Immunology Unit, UCL Cancer Institute, UCL, London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Śledzińska
authors.affiliation: Cancer Immunology Unit, UCL Cancer Institute, UCL, London, UK.
authors.forename: Laurie
authors.initials: L
authors.lastname: Menger
authors.affiliation: Cancer Immunology Unit, UCL Cancer Institute, UCL, London, UK.
authors.forename: Katharina
authors.initials: K
authors.lastname: Bergerhoff
authors.affiliation: Cancer Immunology Unit, UCL Cancer Institute, UCL, London, UK. Electronic address: k.peggs@ucl.ac.uk.
authors.forename: Karl S
authors.initials: KS
authors.lastname: Peggs
authors.affiliation: Cancer Immunology Unit, UCL Cancer Institute, UCL, London, UK. Electronic address: s.quezada@ucl.ac.uk.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Quezada
mesh_terms: D000818:Animals; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*
keywords: CTLA-4; Cancer immunotherapy; Inhibitory checkpoints; Inhibitory receptors on T cells; PD-1