Mechanisms of paraneoplastic neurological syndromes

Purpose of review – This review describes the mechanisms of paraneoplastic neurological syndromes (PNS) and the recent advances underlying these. Recent findings – This review covers advances in the understanding of the immunobiology of PNS. Specifically, evidence that PNS associated with antibodies against intracellular antigens are T-cell mediated processes, of interferon-γ signaling, major histocompatibility complex (MHC) class I upregulation, and granzyme mediated neuronal death. In contrast, PNS with antibodies against neuronal surface antigens are antibody-mediated and cause reversible neuronal dysfunction. Further, the perennial question of why only few patients develop these disorders is emerging from studies of tumor genomics and host HLA associations. Finally, immune checkpoint inhibitors have demonstrated the role of immune tolerance breakdown in the development of these disorders. Summary – These advancements in understanding of mechanisms of PNS have several implications for clinical practice and research. For clinical practice, these findings may lead to prognostication of risk of PNS in cancer patients and potential novel therapeutic approaches. For research, these findings have important implications for understanding tumor immunology, and immune tolerance.