Abstract Details

Title CSF Specific T Cell Activation Characterizes Neurological Immune-related Adverse Events Following Immune Checkpoint Inhibitor Therapy

Topic Autoimmune Neurology

Presentation(s) S38 - Autoimmune Neurology: Peripheral Autoimmunity, Paraneoplastic Disease, Checkpoint Inhibitors, and Neurosarcoidosis (4:30 PM-4:42 PM)

Poster/Presentation
Number 006

Background While immune checkpoint inhibitors (ICI) have revolutionized cancer therapy, they are associated with a severe risk of irAE. Neurological irAE (NirAE) often manifest as ICI associated polyneuropathy (ICI PNP) with rapidly progressive and severe sequelae similar to Guillain-Barré syndrome (GBS).

Objective We aimed to identify mechanisms of immune checkpoint inhibitor associated neurological immune related adverse events (irAE) by studying their immune cell composition.

Design/Methods Using retrospective collection of flow cytometry data (n=43), we investigated the immune cell composition of paired cerebrospinal fluid (CSF) and blood NirAE samples of NirAEs, non-neurological irAEs and no irAE. We additionally stratified ICI PNP patients by flow cytometry and single cell sequencing and compared them to differential diagnosis such as confirmed tumor progression and Guillain-Barré Syndrome.

Results

We detected a disease-specific cellular composition of CSF cells of NirAE patients. CSF specific T cells activation occurred only in NirAE patients but not in other irAE patients. A significant increase in CD4⁺ and CD8⁺ T cell activation can distinguish ICI PNP patients compared to GBS patients and provides first evidence of a possible discriminatory biomarker. Transcriptionally activated CD 8 T cells were more abundant in the CSF compared to control and showed an increase in cytotoxic differentially expressed genes.

Conclusions Strong T cell activation in the CSF only occurs when T cell-mediated irAE affect the nervous system. The organ specificity of ICI-autoimmunity may thus be determined also by the site of T cell disinhibition. This provides a clinically relevant biomarker that can distinguish ICI PNP from differential diagnosis and possibly guide further treatment decisions.

Authors/Disclosures
Louisa Müller-Miny PRESENTER	No disclosure on file
Svea Haessner	No disclosure on file
Frederike Straeten	No disclosure on file
Andreas Schulte-Mecklenbeck	No disclosure on file
Heinz Wiendl, MD, FAAN (University of Muenster)	Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Johnson&Johnson / Janssen. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Wiendl has received personal compensation in the range of $0-$499 for serving as a Consultant for Idorsia. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Immunic. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NexGen. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Worldwide Clinical Trials. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BD. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gossamer Bio. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for LTS. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Samsung. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sangamo. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz-Hexal. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cellerys. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dianthus. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Toleranzia. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Uniqure. The institution of Dr. Wiendl has received research support from Biogen. The institution of Dr. Wiendl has received research support from Roche. The institution of Dr. Wiendl has received research support from Deutsche Forschungsgemeinschaft. The institution of Dr. Wiendl has received research support from European Union. The institution of Dr. Wiendl has received research support from Argenx. The institution of Dr. Wiendl has received research support from CSL Behring. The institution of Dr. Wiendl has received research support from Merck. The institution of Dr. Wiendl has received research support from UCB. Dr. Wiendl has received publishing royalties from a publication relating to health care. Dr. Wiendl has received publishing royalties from a publication relating to health care.
Oliver Grauer	No disclosure on file
Gerd Meyer Zu Horste, MD (University Hospital Muenster)	Dr. Meyer Zu Horste has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for LFB. The institution of Dr. Meyer Zu Horste has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Meyer Zu Horste has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. The institution of Dr. Meyer Zu Horste has received research support from Merck KGaA. The institution of Dr. Meyer Zu Horste has received research support from Roche. Dr. Meyer Zu Horste has received intellectual property interests from a discovery or technology relating to health care.