About this Research Topic
The activity of the immune system is finely modulated by mechanisms that contribute to self-tolerance and prevent autoimmunity. For instance, immune checkpoints, including proteins such as cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death receptor-1 (PD-1), and its associated ligand (PD-L1), are crucial regulators of T cells. These proteins can downregulate T cell activation, which is fundamental to suppress an excessive response like the one seen in autoimmune disorders. However, immune checkpoints are also part of the mechanisms by which cancer cells can escape immune surveillance. The advent of cancer immunotherapy with monoclonal antibodies targeting these immune checkpoints (immune checkpoint inhibitors, ICIs) was a breakthrough in oncology, as ICIs can stimulate the patient’s own T cells to fight cancer. Unfortunately, the use of ICIs is associated with a spectrum of unique and potentially severe toxicities known as immune-related adverse events (irAEs), which can affect any organ or system, including the nervous system in approximately 1-3% of patients.
Given their rarity, neurological toxicities are among those with less available data in terms of risk factors, predictive and diagnostic biomarkers, immunopathogenesis, clinical presentations, treatment approaches, and long-term outcomes. Nevertheless, as ICIs use is rapidly expanding with more than 20 oncological indications to date, it is very important to expand our knowledge on neurological irAEs, which can be severe or even fatal in a substantial proportion of patients. The main problem we aim to address in this Research Topic is how the activation of T cells induced by ICIs contributes to central and peripheral neurological autoimmunity. Additionally, we seek to translate this knowledge to better understand non-ICI related neuroimmune conditions and to apply precision medicine strategies for the early identification and treatment of affected patients without compromising oncological outcomes.
The central goal of this Research Topic is to provide a more precise understanding of the various (common and novel) neurological irAEs of ICIs. We welcome the submission of Original Research, Review, Mini-Review, Methods, Case report, and Perspective articles that cover, but are not limited to the following topics:
• Clinical presentation and epidemiology of neurological irAEs.
• Differential diagnosis of neurological irAEs with other more frequent conditions that can cause neurological symptoms in patients with systemic cancer, including direct neoplastic invasion (i.e., metastasis and leptomeningeal dissemination), metabolic and infectious complications, and other iatrogenic (non-immune-related) disorders.
• Insights from pathological and autopsy studies involving patients with neurological irAEs, along with comparison with pathological data from paraneoplastic neurological syndromes.
• Evaluation of potential biomarkers for predicting, diagnosing, or assessing the outcome of neurological irAEs.
• Addressing the value of neuronal antibodies before and during treatment with ICIs in predicting toxicities and efficacy of cancer immunotherapy.
• Elucidating the mechanisms underlying these toxicities.
• Assessing the safety and efficacy of rechallenge after neurological irAEs.
• Long-term neurological and oncological outcomes.
Please note that Prof. Alberto Vogrig received speaker honoraria from Angelini, Bristol Myers Squibb, and Lusofarmaco.
Also note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.
Given their rarity, neurological toxicities are among those with less available data in terms of risk factors, predictive and diagnostic biomarkers, immunopathogenesis, clinical presentations, treatment approaches, and long-term outcomes. Nevertheless, as ICIs use is rapidly expanding with more than 20 oncological indications to date, it is very important to expand our knowledge on neurological irAEs, which can be severe or even fatal in a substantial proportion of patients. The main problem we aim to address in this Research Topic is how the activation of T cells induced by ICIs contributes to central and peripheral neurological autoimmunity. Additionally, we seek to translate this knowledge to better understand non-ICI related neuroimmune conditions and to apply precision medicine strategies for the early identification and treatment of affected patients without compromising oncological outcomes.
The central goal of this Research Topic is to provide a more precise understanding of the various (common and novel) neurological irAEs of ICIs. We welcome the submission of Original Research, Review, Mini-Review, Methods, Case report, and Perspective articles that cover, but are not limited to the following topics:
• Clinical presentation and epidemiology of neurological irAEs.
• Differential diagnosis of neurological irAEs with other more frequent conditions that can cause neurological symptoms in patients with systemic cancer, including direct neoplastic invasion (i.e., metastasis and leptomeningeal dissemination), metabolic and infectious complications, and other iatrogenic (non-immune-related) disorders.
• Insights from pathological and autopsy studies involving patients with neurological irAEs, along with comparison with pathological data from paraneoplastic neurological syndromes.
• Evaluation of potential biomarkers for predicting, diagnosing, or assessing the outcome of neurological irAEs.
• Addressing the value of neuronal antibodies before and during treatment with ICIs in predicting toxicities and efficacy of cancer immunotherapy.
• Elucidating the mechanisms underlying these toxicities.
• Assessing the safety and efficacy of rechallenge after neurological irAEs.
• Long-term neurological and oncological outcomes.
Please note that Prof. Alberto Vogrig received speaker honoraria from Angelini, Bristol Myers Squibb, and Lusofarmaco.
Also note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.
Keywords: Neurological toxicities, Neurological adverse events, Immune checkpoint inhibitors, Cancer immunotherapy, Autoimmune encephalitis, Paraneoplastic neurological syndrome, Myositis, Myasthenia gravis
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
