Team: Juan Garcia Vallejo, Filip Eftimov, Mariette Labots, Joep Killestein, Tanja de Gruijl

ImNDs, including Guillain-Barré syndrome (GBS), myasthenia gravis (MG), idiopathic inflammatory myopathy (IIM), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and multiple sclerosis (MS), exhibit diverse clinical manifestations. However, their underlying immunopathology remains poorly understood, and treatment responses vary significantly. This suggests the presence of individual-specific rather than disease-specific mechanisms, offering potential for personalized medicine.
Similarly, irAEs present a major challenge in cancer immunotherapy, affecting 3-5% of immune checkpoint inhibitor (ICI) patients and ~40% of CAR T-cell recipients. These immune complications can mimic imNDs and often necessitate treatment discontinuation, high-dose steroids, and hospitalization. While various mechanisms—such as antigen mimicry and cytokine dysregulation—have been proposed, no reliable biomarkers exist to predict which patients will develop irAEs.
Leveraging advanced immunophenotyping techniques, this project will analyze over 200 immune parameters to define distinct immunotypes in imNDs and irAEs. Building on recent research demonstrating the predictive potential of circulating immune cells in cancer patients, our study aims to establish a novel immune-based classification system. This will pave the way for improved diagnostics and targeted treatment strategies, ultimately advancing personalized medicine in both neuroinflammation and oncology.

The aim of this project is to characterize common and distinct immunological pathomechanisms in immune-mediated neuroinflammatory diseases (imNDs) and immune-related adverse events (irAEs) of cancer immunotherapy. This overarching goal can be further subdivided in the following specific aims:

• (Re)define imNDs and irAEs based on immunologic cellular signatures (immunotypes) to allow future patient-tailored treatments.
• Provide a detailed clinical and immunological and clinical characterization of imNDs and irAEs.
• Refine identified biomarkers into actionable diagnostic/predictive tests in both imNDs and irAEs.
• Characterize immunological changes in response to CAR T-cell therapy and correlate changes with occurrence of cytokine release syndrome (CRS) and Immune-effector Cell-Associated Neurotoxicity Syndrome (ICANS).