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. 2025;103(10):930-933.
doi: 10.1159/000543949. Epub 2025 Feb 25.

Retrospective Analysis: S100 as Marker for Immune Effector Cell-Associated Neurotoxicity Syndrome

Axel Schulenburg, Axel Schulenburg  1 , Lina Rüsing  1 , Armin Bumberger  1 , Margit Mitterbauer  1 , Julia Cserna  1 , Clemens Petrasch  1 , Sophia Oesterreicher  2 , Nina Worel  2 , Werner Rabitsch  1
Affiliations

Retrospective Analysis: S100 as Marker for Immune Effector Cell-Associated Neurotoxicity Syndrome

Axel Schulenburg et al. Oncology. 2025.

Abstract

Introduction: Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for hematologic malignancies, offering significant therapeutic benefits. However, this therapy is also associated with adverse effects such as cytokine release syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which can lead to severe neurological symptoms. The pathophysiology of ICANS remains unclear but is believed to involve immune-mediated inflammation in the brain. This study investigates the potential of S100, a protein marker associated with blood-brain barrier integrity, as an early indicator of ICANS.

Methods: We retrospectively analyzed daily blood samples for S100 levels in patients undergoing CAR T-cell therapy, correlating these levels with the onset and severity of ICANS.

Results: The results show that S100 levels significantly increased in patients who developed ICANS, with a positive correlation between the duration of elevation and the severity of the neurological symptoms.

Conclusion: These findings suggest that S100 may serve as a useful biomarker for early detection of ICANS and could potentially guide therapeutic interventions. However, further studies are needed to fully understand its prognostic value in this context.

Keywords: Chimeric antigen receptor T-cell therapy; ICANS; Marker; S100; Side effects.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Aggregated (sum of) patients with elevated S100 and patients suffering from ICANS as well as the mean S100 level over time, respectively.
See this image and copyright information in PMC

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