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Updated: Aug 9, 2025
Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity
Published on: October 25, 2016
Monocyte chemoattractant protein 1 as a potential biomarker for immune checkpoint inhibitor-associated neurotoxicity
Nora Möhn1, Susann Mahjoub1, Laura Duzzi1
1Department of Neurology, Hannover Medical School, Hannover, Germany.
Background:
Oncological patients can benefit substantially from treatment with immune checkpoint inhibitors (ICI). However, there is a growing awareness of immune-related adverse events (irAE). Especially ICI-mediated neurological adverse events (nAE(+)), are tough to diagnose and biomarkers to identify patients at risk are missing.
Methods:
A prospective register with prespecified examinations was established for ICI treated patients in December 2019. At the time of data cut-off, 110 patients were enrolled and completed the clinical protocol. Herein, cytokines and serum neurofilament light chain (sNFL) from 21 patients were analyzed.
Results:
nAE of any grade were observed in 31% of the patients (n = 34/110). In nAE(+) patients a significant increase in sNFL concentrations over time was observed. Patients with higher-grade nAE had significantly elevated serum-concentrations of monocyte chemoattractant protein 1 (MCP-1) and brain-derived neurotrophic factor (BDNF) at baseline compared to individuals without any nAE (p < 0.01 and p < 0.05).
Conclusion:
Here, we identified nAE to occur more frequently than previously reported. Increase of sNFL during nAE confirms the clinical diagnosis of neurotoxicity and might be a suitable marker for neuronal damage associated with ICI therapy. Furthermore, MCP-1 and BDNF are potentially the first clinical-class nAE predictors for patients under ICI therapy.
Insights
Immune checkpoint inhibitors (ICI) can cause neurological adverse events (nAE). Serum neurofilament light chain (sNFL) increase indicates neuronal damage, while MCP-1 and BDNF may predict nAE risk in cancer patients.
Area of Science:
- Oncology
- Immunology
- Neurology
Background:
- Immune checkpoint inhibitors (ICI) offer significant oncological benefits.
- Immune-related adverse events (irAE), particularly neurological adverse events (nAE), pose diagnostic challenges.
- Biomarkers for identifying patients at risk of nAE are currently lacking.
Purpose of the Study:
- To investigate potential biomarkers for predicting and diagnosing ICI-mediated neurological adverse events (nAE).
- To assess the frequency and clinical characteristics of nAE in patients treated with ICI.
Main Methods:
- Prospective enrollment of 110 ICI-treated patients into a dedicated registry.
- Analysis of serum cytokines, including monocyte chemoattractant protein 1 (MCP-1) and brain-derived neurotrophic factor (BDNF), and serum neurofilament light chain (sNFL) in 21 patients.
- Comparison of biomarker levels between patients with and without nAE.
Main Results:
- Neurological adverse events (nAE) were observed in 31% of patients.
- A significant increase in sNFL over time was noted in patients experiencing nAE.
- Elevated baseline levels of MCP-1 and BDNF were significantly associated with higher-grade nAE.
Conclusions:
- nAE occur more frequently than previously reported.
- Increased sNFL serves as a potential marker for ICI-associated neurotoxicity and neuronal damage.
- MCP-1 and BDNF show potential as early predictive biomarkers for nAE in patients undergoing ICI therapy.
