Chimeric antigen receptor (CAR)-T cell therapy is a groundbreaking form of cancer treatment that involves reprogramming a patient’s T cells to recognize and attack cancer cells. This personalized immunotherapy has shown remarkable success in treating certain types of blood cancers, such as leukemia and lymphoma [1,2,3]; however, one of the potential side effects of CAR‑T cell therapy is the development of a condition called immune effector cell-associated neurotoxicity syndrome (ICANS) [4]. This can cause symptoms such as confusion, delirium, seizures, and other neurological issues. While the exact cause of ICANS is not fully understood, it is believed to be related to the immune response triggered by the CAR‑T cells, leading to inflammation in the brain. Medical professionals closely monitor patients undergoing CAR‑T cell therapy for signs of ICANS and have developed protocols to manage and treat this potential side effect [5, 6]. Research in this area is ongoing to better understand, prevent, and treat ICANS, allowing for the continued advancement of CAR‑T cell therapy as a promising cancer treatment.

Therefore, it would be highly desirable if there were a factor that correlates with the occurrence of ICANS. This could help predict which patients are at high risk of developing this side effect. It could also be useful in tailoring ICANS therapy. In this context, we came across a marker called S100. The blood marker S100 is used to diagnose and monitor the progression of certain diseases. It refers to a group of proteins that occur in various tissues of the body, including the nervous system. The S100 proteins can be measured in blood tests and serve as indicators of various conditions. The importance of S100 lies mainly in neurology and oncology. In neurology, an increased S100 value can indicate damage to the brain or spinal cord, for example, after stroke, injury, or neurodegenerative disease. In oncology, the S100 value can be helpful in diagnosing and monitoring melanomas and other types of cancer.

Of particular interest to us was that S100 is also a marker for a damaged blood-brain barrier [7]. In addition to their diagnostic significance, S100 proteins play various biological roles. They are calcium-binding proteins that modulate cellular functions such as proliferation, differentiation, and apoptosis [8]. They act as inflammatory mediators, participate in interactions between neurons and glial cells, serve as markers for tissue damage, and indicate the integrity of the blood-brain barrier [9]. Understanding these functions can further clarify the role of S100 in diagnostics and treatment. To evaluate the correlation of this marker with ICANS, we monitored it daily in a series of patients who underwent CAR‑T cell therapy at our institution.