Abstract
The mechanism(s) of immune checkpoint inhibitor (ICI)-induced myasthenia gravis (MG), an immune-related adverse event (irAE) that is fatal and limits subsequent ICI use, remain unexplored. Here, through comparative genomic analysis, we identified a pathogenic p.S467C germline variant inSLC22A5in a thymoma case with ICI-induced MG, which was found to be associated with fatty acid oxidation through its regulation on L-carnitine levels. Remarkably, ICI rechallenge with L-carnitine pretreatment led to durable response without MG-related symptoms. Thus, we provide the first clinical evidence of genetic test-directed irAE management, which integrates individualized ICI treatment into the evolving paradigm of cancer management.
Funder
the Medical Important Talents of Jiangsu Province
Jiangsu Provincial Key Research and Development Program
National Natural Science Foundation of China
Natural Science Foundation of Jiangsu Province
Subject
Cancer Research,Pharmacology,Oncology,Molecular Medicine,Immunology,Immunology and Allergy
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