Paraneoplastic neurological syndromes: from diagnosis to therapeutic approaches

Paraneoplastic neurological syndromes (PNS) result from an autoimmune response against neural self-antigens which are ectopically expressed in neoplastic cells. Approximately 1 out of 300 patients with cancer develop PNS. In the present work, updated diagnostic criteria and recommendations are reported to increase knowledge of clinical, immunological, and oncological heterogeneity of these disorders. The crucial role of neuronal antibodies as biomarkers in the clinical laboratory practice is also discussed. The thesis especially focuses on research approaches, based on high-resolution epitope mapping and analysis of antigenic signature by phage immunoprecipitation sequencing, as tools to better understand the onco-immunological crosstalk process, loss of self-tolerance and triggers potentially involved in the pathogenesis of PNS. Lastly, a potential therapeutic target in paraneoplastic cerebellar degeneration (PCD), namely IFN-y, is described. The latter is expressed by cerebellum-infiltrating T cells and treatment using the anti-IFN-y antibody in a mouse model of PCD is reported to protect from neuronal damage almost completely, suggesting a new therapeutic opportunity for cancer patients at the onset of paraneoplastic neurological disorders.