Immune signatures of immune checkpoint inhibitor-induced neurological immune related adverse events - confirmatory data set

Neurological immune related adverse events (irAE-n) are an increasingly recognized complication of immune checkpoint inhibitor (ICI) treatment. To overcome diagnostic and therapeutic challenges, a better mechanistic understanding of irAE-n is paramount.
Conclusion:
Results: During acute illness, patients with irAE-n presented higher frequencies of CD8+ effector memory type (EM-)1 T cells compared to controls. Presence of multiple immunotoxicities was associated with higher CD8+ EM1 T cell counts. While there were no B cell changes in the overall cohort, we detected a marked decrease of IgD-CD11c+CD19highCD20highCD21low B cells and IgD-CD24+CD21high B cells in a subgroup of patients with ICI-induced autoantibody-positive irAE-n. We further identified signatures indicative of enhanced chemotaxis, inflammation, and angiogenesis in irAE-n patients and discovered CXCL10 as a marker candidate to diagnose and potentially predict irAE-n. Conclusions: We demonstrate profound and partly subgroup-specific immune cell dysregulations in irAE-n patients, which may guide future biomarker development and targeted treatment approaches.
Notes:
This is the confirmatory data set Methods: In this observational cohort study, we collected serum samples and PBMCs from 35 consecutive cancer patients with irAE-n (n = 3 pre-ICI, n = 35 post-ICI) and 43 cancer control patients without high-grade neurological or non-neurological irAEs (n = 43 pre- and post-ICI). Patients received either anti-programmed cell death protein (PD)-1 or anti-PD ligand-1 monotherapy or anti-PD-1/anti-cytotoxic T-lymphocyte associated protein-4 combination therapy. Most common tumor entities were melanoma, lung cancer and hepatocellular carcinoma. Peripheral blood immune profiling was performed using 48-marker mass cytometry and a multiplexed cytokine assay. titrated antibodies spillover compensation 4 elements EQ bead normalization anchor control based batch normalization cryopreserved antibody cocktails