Lung cancer is the most common cancer type worldwide, with one of the highest mortality rates across all cancer types. Cancer immunotherapeutics such as immune checkpoint inhibitors (ICIs) have improved cancer treatment by promoting the body’s natural immune response to tumor development while avoiding toxic effects associated with traditional cytotoxic chemotherapy. However, immunotherapies have been associated with unique toxic effects similar to autoimmune disorders known as immune-related adverse events (irAEs). 4.2% of immunotherapy-treated cancer patients reportedly developed neurological irAEs. In this review, different immunotherapies were studied, including ICIs and mechanism-specific novel therapies, in order to determine a combination therapy to most effectively mitigate the development of neurotoxicities, e.g. encephalitis, in patients with Non-small Cell Lung Cancer (NSCLC). Reviews were examined discussing the outcomes of monotherapy and combination therapy with ICIs in cancer types such as melanoma and NSCLC, and studies where immune antitumor response was enhanced using antibodies against specific elements of the immune system, such as Regulatory T cells and Interleukin-6 (IL-6), were investigated. Existing immunosuppressive treatments used to resolve neurotoxicities were also examined. Many ICIs were associated with neurotoxicities and varied treatment responses, but certain ICI combinations led to durable antitumor responses with relatively milder toxicity. Novel blockade of immune mechanisms can increase antitumor activity without directly targeting immune effector cells, and second-line immunosuppressives can resolve irAEs when they arise. Though research suggests certain treatment regimens are more effective with relatively lower associated toxicity, treatments such as CCL1/CCR8 antibody blockade have only shown results in mouse and in vitro models. Novel antibodies will need to undergo clinical trials before the use of these antibodies is considered in cancer patients, and few studies have investigated the use of immunosuppressives used to treat adverse events, such as rituximab, in combination with first-line immunotherapeutics.
Keywords: non-small cell lung cancer, immunotherapy, immune-related adverse event, neurotoxicity, immune checkpoint inhibition, monoclonal antibodies, encephalitis, PD-1, CTLA-4
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