What is it about?
Immune checkpoint inhibitors (ICIs) can trigger an anti-tumor immune response by blocking cytotoxic inhibitory signaling. Some of them are well recognized to affect tumor eliminating effects such as CTLA-4, PD-1 on T cells, and PD-L1 on tumor cells. The use of ICIs may be of benefit to patient survival and they have become parts of the standard treatment in a number of human malignancies, resulting in a substantial increase in the number of patients receiving ICI-therapy over the last couple of years. Although ICIs play critical roles against tumors, the activation of T cells shows the potential to make host organ systems suffer from autoimmune adverse effects. With the increase in indications and widespread use of ICI-therapy, concerns have arisen about the occurrence and development of neurotoxic adverse effects. Neurological irAEs (nAEs) are not very common, accounting for no more than 3% in all irAEs. NAEs are rare but can be severe, so it’s significant for doctors to diagnose and take measures as early as possible. We summarized various nAEs, including meningitis, encephalitis, and hypophysitis in the central nervous system, and myositis, myasthenia gravis, and peripheral neuropathies in the peripheral system. We also reviewed the current diagnosis and treatment methods for nAEs commonly used in clinical practice.
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Why is it important?
Immune checkpoint inhibitors (ICIs) have recently been used as a promising treatment for cancer, while their toxicity and immune-related side effects can be seen in any organ, including the nervous system. In contrast to other immune-related adverse events (irAEs), neurological irAEs (nAEs) are rare, with varying incidence and symptom complexity. Although nAEs are uncommon, they can sometimes be severe and even lead to death. However, little attention has been paid to nAEs, and the literature is mostly clinical reports with only a few cases.
Perspectives
Cancer immunotherapy and associated neurotoxicity offer opportunities for collaboration between oncologists and neurologists. We hope that this work will contribute to the understanding of nAEs. There is still a lot to learn, such as whether and why patients with nAEs respond better to ICI-therapy. The mechanisms and significance of nAEs need to be fully clarified to address these issues and optimize the treatment strategy. For individual ICIs, better defining the patterns of neurotoxicity, elucidating the possible mechanism, working out potential biomarker and refining therapeutic options, are all worthy of attention in future studies.
Lei Shi
Chongqing University
Read the Original
This page is a summary of: Immune Checkpoint Inhibitors and Neurotoxicity, Current Neuropharmacology, August 2021, Bentham Science Publishers,
DOI: 10.2174/1570159x19666201230151224.
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