Autoimmune Complications of Modern Cancer Therapies

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Background

Oncology has evolved tremendously in recent years. In addition to classical chemotherapeutic agents, there are more and more therapies that stimulate the immune system to target tumor cells. The leading examples are certainly immune checkpoint inhibitors (ICI). By activating cytotoxic T cells, they can induce remarkable anti-tumor effects. Even in tumor diseases with previously markedly poor prognosis- such as metastatic malignant melanoma and non-small cell lung cancer - impressive survival rates have been achieved. The same is true for CAR T-cell therapy, which has been approved primarily for diffuse large B-cell lymphoma. However, often these convincing successes are accompanied by potentially serious side effects. In ICI therapy, these are autoimmune adverse events that potentially affect any organ and typically present as hepatitis, colitis, dermatitis, or pneumonitis. The nervous system can also be affected, and these complications are particularly difficult to diagnose and treat. The most important CAR T-cell associated toxicities are cytokine-release syndrome and neurotoxicity. Pathogenetically, CRS is mainly caused by the release of effector cytokines, in particular IL-6, which in turn recruit macrophages and other immune cells and thus maintain the excessive immune response. The etiology of neurotoxicity is less clear; discussed are recognition of cryptic CNS antigens by CAR T-cells and off-target cytotoxicity. Due to an increase in immunotherapies and their indications, practitioners will have to deal with these complications to an increasing extent in the future.

Although knowledge about modern cancer therapies and their potential immunological complications continues to increase, many research questions remain unanswered. Neurological side effects in particular have not been adequately studied to date. We are aiming to strengthen our understanding of pathophysiological mechanisms and our ability to detect biomarkers for the development of l adverse autoimmune events, especially neurological ones. By developing a risk stratification for adverse events, the individually appropriate therapy could be found for each patient after detailed consideration of benefits and hazards. Additionally, treatment approaches to counteract immunological complications will be evaluated and therapeutic recommendations will be further advanced.

This Research Topic will provide an overview of autoimmune related complications based on a wide variety of immunotherapeutics in oncology. These include for example, ICI-associated immune-related adverse events as well as toxicity due to CAR T-cell therapy or side effects caused by targeted therapies. In particular, the focus should be on neurological side effects. We hope to stimulate an interesting conversation and increase the knowledge about this current and promising topic.

We welcome the submission of Original Research, Review/Mini-Review and Case Report articles that involve all aspects of autoimmune complications of modern cancer therapies, focusing on, but not limited to:

• Characterization
• Diagnosis
• Pathomechanisms
• Biomarkers
• Treatment

Keywords: -Immune checkpoint inhibition, Neurotoxicity, Autoimmune adverse events, Immune related adverse events (irAE), CAR T-cell therapy, ICANS

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.

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