Monocyte chemoattractant protein 1 as a potential biomarker for immune checkpoint inhibitor-associated neurotoxicity

Cancer Med. 2023 Apr;12(8):9373-9383. doi: 10.1002/cam4.5695. Epub 2023 Feb 16.

Abstract

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.

Keywords: biomarker; immune-related adverse events; immunotherapy; neurotoxicity; serum neurofilament light chains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Brain-Derived Neurotrophic Factor*
  • Chemokine CCL2
  • Cytokines
  • Humans
  • Immune Checkpoint Inhibitors* / adverse effects

Substances

  • Immune Checkpoint Inhibitors
  • Brain-Derived Neurotrophic Factor
  • Chemokine CCL2
  • Biomarkers
  • Cytokines