title: Targeting the T-cell co-stimulatory CD27/CD70 pathway in cancer immunotherapy: rationale and potential.
abstract: In 2013, cancer immunotherapy was named 'breakthrough of the year' based on the outcome of clinical trials with blocking antibodies to the T-cell co-inhibitory receptors CTLA-4 and PD-1. This success has emphasized that cytotoxic T-cell responses to cancer can occur, but are limited by peripheral tolerance and by immunosuppression in the tumor microenvironment. Targeting of CTLA-4, PD-1 or its ligands partly overcomes these limitations and can now be applied in multiple immunogenic cancer types. Furthermore, an increased success rate is expected from combining CTLA-4 and/or PD-1 blocking with deliberate engagement of T-cell co-stimulatory receptors, particularly TNF receptor (R) family members. The TNFR family includes CD27 (Tnfrsf7), for which an agonistic antibody has recently entered clinical trials. In this review, we describe how CD27 co-stimulation impacts the T-cell response, with the purpose to illuminate how CD27 agonism can be exploited in cancer immunotherapy.
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: van de Ven
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Jannie
authors.initials: J
authors.lastname: Borst
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D053282:CD27 Ligand / Q000037:antagonists & inhibitors* / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D053282:CD27 Ligand; C505771:CD70 protein, human; D060908:CTLA-4 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
keywords: TNF receptor family; antibody; cancer; co-inhibition; co-stimulation; cytotoxic T cell; immunotherapy; ipilimumab; nivolumab