INSIGHTS INTO NEUROLOGICAL IMMUNE-RELATED ADVERSE EVENTS ASSOCIATED WITH IMMUNE CHECKPOINT INHIBITOR CANCER THERAPY

The development of immune checkpoint inhibitors (ICI) has revolutionised cancer therapy. However, the use of ICIs may lead to the development of immune-related adverse events (irAEs), resulting in severe disability, interruption of cancer therapy, and even death. Neurological irAEs occur in 1-10% of ICI-treated patients and can be associated with antibodies (Abs) binding to neuronal or glial antigens. We studied the presence of immunoglobulin G (IgG) and IgM Abs targeting different neuroglial antigens in the serum of 169 cancer patients prior to and after ICI treatment. We found IgG Abs targeting neuronal proteins in 21/169 (12%) of our patient cohort post ICI treatment compared to 1/59 (1.7%, p=0.019) of controls. Out of the Ab positive patient samples, 48% were attributed to Abs recognising cell surface proteins and 52% had Abs binding to intracellular targets. Importantly, 58% of patients that were Ab positive after ICI therapy already had Abs targeting the same protein prior to ICI initiation. 23% developed de novo Abs after ICI treatment and 15% presented with Abs only before ICI therapy (Fig.). The high proportion of patients with specific neuronal IgG prior to and after ICI administration raises implications for undertaking screening of patients before receiving ICIs to develop a more personalised risk profile. Correlation with clinical manifestations, evaluation of IgM positivity, and defining functional effects of IgGs in comparison to their idiopathic counterparts are underway. Understanding the underlying immunobiology will contribute to predicting complications from ICIs, enabling personalised treatment to improve patient survival and quality of life.