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Pr Roland Liblau CPTP, Toulouse – Immune checkpoint blockade, neuroinflammation and paraneoplastic neurological disease
13 décembre 2019 @ 11:00 - 12:00
Paraneoplastic neurologic disorders (PND) are immune-mediated neurological diseases that develop in the setting of malignancy. The target onconeural antigens are expressed physiologically by neurons, and aberrantly by certain tumor cells. These tumor-associated antigens can be presented to T cells, generating an antigen-specific immune response that leads to autoimmunity within the nervous system.
In an animal model, in which a neo-self-antigen was expressed in both Purkinje neurons and implanted breast tumor, immune checkpoint blockade led to complete tumor control at the expense of cerebellum infiltration by T cells and Purkinje neuron loss, thereby mimicking PND. Our findings strongly suggest that the production of IFNg by cerebellum-invading T cells plays a major role in Purkinje neuron death. Our successful pre-clinical use of neutralizing anti-IFNg antibody for the treatment of PCD offers a new therapeutic opportunity for cancer patients at the onset of paraneoplastic neurological disorders.
Incidentally, the induction of a cellular immune response within the nervous system through immune checkpoint blockade led us and others to test this approach in the context of chronic JC virus infection in immunocompromised patients.