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Vogrig A, Muñiz-Castrillo S, Desestret V, et al. Pathophysiology of paraneoplastic and autoimmune encephalitis: genes, infections, and checkpoint inhibitors. Ther Adv Neurol Disord. 2020;13:1756286420932797doi: 10.1177/1756286420932797.
Vogrig, A., Muñiz-Castrillo, S., Desestret, V., Joubert, B., & Honnorat, J. (2020). Pathophysiology of paraneoplastic and autoimmune encephalitis: genes, infections, and checkpoint inhibitors. Therapeutic advances in neurological disorders, 131756286420932797. https://doi.org/10.1177/1756286420932797
Vogrig, Alberto, et al. "Pathophysiology of paraneoplastic and autoimmune encephalitis: genes, infections, and checkpoint inhibitors." Therapeutic advances in neurological disorders vol. 13 (2020): 1756286420932797. doi: https://doi.org/10.1177/1756286420932797
Vogrig A, Muñiz-Castrillo S, Desestret V, Joubert B, Honnorat J. Pathophysiology of paraneoplastic and autoimmune encephalitis: genes, infections, and checkpoint inhibitors. Ther Adv Neurol Disord. 2020 Jun 24;13:1756286420932797. doi: 10.1177/1756286420932797. eCollection 2020. PMID: 32636932; PMCID: PMC7318829.
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Ther Adv Neurol Disord. 2020 Jun 24;13:1756286420932797. doi: 10.1177/1756286420932797. eCollection 2020.

Pathophysiology of paraneoplastic and autoimmune encephalitis: genes, infections, and checkpoint inhibitors.

Therapeutic advances in neurological disorders

Alberto Vogrig, Sergio Muñiz-Castrillo, Virginie Desestret, Bastien Joubert, Jérôme Honnorat

Affiliations

  1. French Reference Center for Paraneoplastic Neurological Syndromes, Hospices Civils de Lyon, Hospital for Neurology and Neurosurgery Pierre Wertheimer, Lyon, France.
  2. Centre de Référence National pour les Syndromes Neurologiques Paranéoplasiques, Hôpital Neurologique, 59 Boulevard Pinel, Bron Cedex, 69677, France.

PMID: 32636932 PMCID: PMC7318829 DOI: 10.1177/1756286420932797

Abstract

Paraneoplastic neurological syndromes (PNSs) are rare complications of systemic cancers that can affect all parts of the central and/or peripheral nervous system. A body of experimental and clinical data has demonstrated that the pathogenesis of PNSs is immune-mediated. Nevertheless, the mechanisms leading to immune tolerance breakdown in these conditions remain to be elucidated. Despite their rarity, PNSs offer a unique perspective to understand the complex interplay between cancer immunity, effect of immune checkpoint inhibitors (ICIs), and mechanisms underlying the attack of neurons in antibody-mediated neurological disorders, with potentially relevant therapeutic implications. In particular, it is reported that ICI treatment can unleash PNSs and that the immunopathological features of PNS-related tumors are distinctive, showing prominent tumor-infiltrating lymphocytes and germinal center reactions. Intriguingly, similar pathological substrates have gained further attention as potential biomarkers of ICI-sensitivity and oncological prognosis. Moreover, the genetic analysis of PNS-associated tumors has revealed specific molecular signatures and mutations in genes encoding onconeural proteins, leading to the production of highly immunogenic neoantigens. Other than PNSs, autoimmune encephalitides (AEs) comprise a recently described group of disorders characterized by prominent neuropsychiatric symptoms, diverse antibody spectrum, and less tight association with cancer. Other triggering factors seem to be involved in AEs. Recent data have shed light on the importance of preceding infections (in particular, herpes simplex virus encephalitis) in inducing neurological autoimmune disorders in susceptible individuals (those with a selective deficiency in the innate immune system). In addition, in some AEs (e.g. LGI1-antibody encephalitis) an association with specific host-related factors [e.g., human leukocyte antigen (HLA)] was clearly demonstrated. We provide herein a comprehensive review of the most recent findings in the field of PNSs and AEs, with particular focus on their triggering factors and immunopathogenesis.

© The Author(s), 2020.

Keywords: CTLA-4; HLA; NMDAR; PD-1; autoimmune encephalitis; immune checkpoint inhibitors; neurological adverse events; paraneoplastic neurological syndromes

Conflict of interest statement

Conflict of interest statement: AV reported receiving a fellowship grant from the European Academy of Neurology (EAN). No other disclosures were reported.

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