title: Conflicting consequences of immunity to cancer versus autoimmunity to neurons: insights from paraneoplastic disease.
abstract: Immunologists are well aware that cancer regression and increased patient survival with the use of checkpoint inhibitors, such as ipilimumab, an antibody directed against cytotoxic T-lymphocyte-associated antigen 4, CTLA-4 (CD152), is accompanied by concomitant autoimmunity. For over 30 years, a small group of investigators have shown that the rare paraneoplastic syndromes are caused by immunity to shared antigens found on both tumors and on components of the nervous system. In this issue of the European Journal of Immunology, Blachère et al. [Eur. J. Immunol. 2014. 44: 3240-3251] elucidate some of the molecular mechanisms underlying the tolerance to neuronal antigens which share epitopes with oncologic antigens, observed in the context of paraneoplastic syndromes in mice. The presence of the shared tumor antigen on a nonhematopoietic cell underlies the basis for a certain level of tolerance in CD4+ and CD8+ T cells, preventing these cells from attacking the brain, but allowing them to lyse the tumor upon transfer into tumor-bearing recipient mice. Comparisons between the paraneoplastic syndromes and the new autoimmune conditions seen with antibodies to immune checkpoints at CD152 or at CD279 are likely to illuminate shared mechanisms and solutions to these vexing diseases.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Steinman
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000276:immunology*; D009474:Neurons / Q000276:immunology*; D020361:Paraneoplastic Syndromes, Nervous System / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D060908:CTLA-4 Antigen; D000939:Epitopes; D061026:Programmed Cell Death 1 Receptor
keywords: Autoimmunity; Cancer; Paraneoplastic neurological disease; Shared antigens; T cells