Immunological Bases of Paraneoplastic Cerebellar Degeneration and Therapeutic Implications.
Animals
Antigens, Neoplasm
/ immunology
Autoantibodies
/ immunology
Autoantigens
/ immunology
Autoimmunity
Cerebellum
/ immunology
Humans
Immunotherapy
/ adverse effects
Neoplasms
/ immunology
Nerve Tissue Proteins
/ immunology
Paraneoplastic Cerebellar Degeneration
/ immunology
Purkinje Cells
/ immunology
Risk Factors
T-Lymphocytes
/ immunology
T cell
animal model
anti-neuronal antibodies
autoimmunity
immunotherapy
paraneoplastic cerebellar degeneration
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
29
02
2020
accepted:
27
04
2020
entrez:
14
7
2020
pubmed:
14
7
2020
medline:
30
3
2021
Statut:
epublish
Résumé
Paraneoplastic cerebellar degeneration (PCD) is a rare immune-mediated disease that develops mostly in the setting of neoplasia and offers a unique prospect to explore the interplay between tumor immunity and autoimmunity. In PCD, the deleterious adaptive immune response targets self-antigens aberrantly expressed by tumor cells, mostly gynecological cancers, and physiologically expressed by the Purkinje neurons of the cerebellum. Highly specific anti-neuronal antibodies in the serum and cerebrospinal fluid represent key diagnostic biomarkers of PCD. Some anti-neuronal antibodies such as anti-Yo autoantibodies (recognizing the CDR2/CDR2L proteins) are only associated with PCD. Other anti-neuronal antibodies, such as anti-Hu, anti-Ri, and anti-Ma2, are detected in patients with PCD or other types of paraneoplastic neurological manifestations. Importantly, these autoantibodies cannot transfer disease and evidence for a pathogenic role of autoreactive T cells is accumulating. However, the precise mechanisms responsible for disruption of self-tolerance to neuronal self-antigens in the cancer setting and the pathways involved in pathogenesis within the cerebellum remain to be fully deciphered. Although the occurrence of PCD is rare, the risk for such severe complication may increase with wider use of cancer immunotherapy, notably immune checkpoint blockade. Here, we review recent literature pertaining to the pathophysiology of PCD and propose an immune scheme underlying this disabling disease. Additionally, based on observations from patients' samples and on the pre-clinical model we recently developed, we discuss potential therapeutic strategies that could blunt this cerebellum-specific autoimmune disease.
Identifiants
pubmed: 32655545
doi: 10.3389/fimmu.2020.00991
pmc: PMC7326021
doi:
Substances chimiques
Antigens, Neoplasm
0
Autoantibodies
0
Autoantigens
0
CDR2 protein, human
0
CDR2L antigen, human
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
991Informations de copyright
Copyright © 2020 Yshii, Bost and Liblau.
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