title: Immune checkpoints and rheumatic diseases: what can cancer immunotherapy teach us?
abstract: The recent success of immune checkpoint blockade in cancer therapy illustrates the importance of the inhibitory receptors cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) in the regulation of antitumour immune responses. However, blocking signalling by these inhibitory immune checkpoint receptors is also associated with substantial inflammatory effects that can resemble autoimmune responses, which is consistent with the role of these receptors in protecting the host from excessive inflammation. The human genome encodes over 300 inhibitory receptors, which represent as many opportunities to modulate inflammation in a disease-specific and tissue-specific manner. We argue that rheumatologists and oncologists should join forces to study these inhibitory immune molecules. An improved understanding of these immune checkpoints will enable both fields to make progress in exploiting inhibitory immune receptors therapeutically. In this Review, we discuss data from studies reporting the adverse inflammatory effects of cancer therapies that target immune checkpoints. We discuss the potential implications of these findings on the biological understanding of autoimmune rheumatic diseases and highlight therapeutic strategies that could be used to target inhibitory receptors for the treatment of these conditions.
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.|Department of Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: van der Vlist
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.|Department of Hematology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Kuball
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.|Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Timothy R D
authors.initials: TR
authors.lastname: Radstake
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.|Department of Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Linde
authors.initials: L
authors.lastname: Meyaard
mesh_terms: D018501:Antirheumatic Agents / Q000276:immunology / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000276:immunology; D019317:Evidence-Based Medicine; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007249:Inflammation / Q000188:drug therapy; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000628:therapy; D061026:Programmed Cell Death 1 Receptor / Q000187:drug effects; D012216:Rheumatic Diseases / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D060908:CTLA-4 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor