Neurologic Autoimmunity in the Era of Checkpoint Inhibitor Cancer Immunotherapy

Anastasia Zekeridou, Vanda A Lennon

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Neurologic autoimmune disorders in the context of systemic cancer reflect antitumor immune responses against onconeural proteins that are autoantigens in the nervous system. These responses observe basic principles of cancer immunity and are highly pertinent to oncological practice since the introduction of immune checkpoint inhibitor cancer therapy. The patient's autoantibody profile is consistent with the antigenic composition of the underlying malignancy. A major determinant of the pathogenic outcome is the anatomic and subcellular location of the autoantigen. IgGs targeting plasma membrane proteins (eg, muscle acetylcholine receptor -IgG in patients with paraneoplastic myasthenia gravis) have pathogenic potential. However, IgGs specific for intracellular antigens (eg, antineuronal nuclear antibody 1 [anti-Hu] associated with sensory neuronopathy and small cell lung cancer) are surrogate markers for CD8+ T lymphocytes targeting peptides derived from nuclear or cytoplasmic proteins. In an inflammatory milieu, those peptides translocate to neural plasma membranes as major histocompatibility complex class I protein complexes. Paraneoplastic neurologic autoimmunity can affect any level of the neuraxis and may be mistaken for cancer progression. Importantly, these disorders generally respond favorably to early-initiated immunotherapy and cancer treatment. Small cell lung cancer and thymoma are commonly associated with neurologic autoimmunity, but in the context of checkpoint inhibitor therapy, other malignancy associations are increasingly recognized.

Original languageEnglish (US)
JournalMayo Clinic proceedings
DOIs
StatePublished - Jan 1 2019

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Autoimmunity
Immunotherapy
Nervous System
Neoplasms
Small Cell Lung Carcinoma
Autoantigens
Autoimmune Diseases of the Nervous System
Cell Membrane
Peptides
Proteins
Thymoma
Myasthenia Gravis
Cholinergic Receptors
Major Histocompatibility Complex
Autoantibodies
Blood Proteins
Anti-Idiotypic Antibodies
Immunity
Membrane Proteins
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Neurologic Autoimmunity in the Era of Checkpoint Inhibitor Cancer Immunotherapy. / Zekeridou, Anastasia; Lennon, Vanda A.

In: Mayo Clinic proceedings, 01.01.2019.

Research output: Contribution to journalReview article

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