title: Pathological characterization of nivolumab-related liver injury in a patient with glioblastoma.
abstract: Immune checkpoint inhibitors such as anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies have dramatically changed the paradigm of cancer therapy over the past few years. The use of these agents is associated with a unique pattern of autoimmune-like/inflammatory side effects termed immune-related adverse events (irAEs), that may cause collateral damage to normal tissues. Although severe irAEs remain rare, they can become life-threatening if not anticipated and managed appropriately. Improving our knowledge of the mechanisms underlying the development of these toxicities is crucial to optimize clinical efficacy and safety of these new immunotherapeutics. Herein we describe for the first time the pathological features of a severe liver-injury associated with the administration of the anti-PD-1 agent nivolumab in a patient with glioblastoma.
authors.affiliation: Humanitas Cancer Center, Humanitas Clinical & Research Center, Via Manzoni 56, 20089 Rozzano (Mi), Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Simonelli
authors.affiliation: Department of Pathology, Humanitas Clinical & Research Center, Via Manzoni 56, 20089 Rozzano (Mi), Italy.|Humanitas University, Via Alessandro Manzoni 113, 20089 Rozzano (Mi), Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Di Tommaso
authors.affiliation: Humanitas Cancer Center, Humanitas Clinical & Research Center, Via Manzoni 56, 20089 Rozzano (Mi), Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Baretti
authors.affiliation: Humanitas Cancer Center, Humanitas Clinical & Research Center, Via Manzoni 56, 20089 Rozzano (Mi), Italy.|Humanitas University, Via Alessandro Manzoni 113, 20089 Rozzano (Mi), Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015551:Autoimmunity; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005909:Glioblastoma / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D009367:Neoplasm Staging; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D025521:Tumor Suppressor Proteins; D000077594:Nivolumab; D003606:Dacarbazine; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide
keywords: anti-PD-1/L-1 agents; hepatitis; immune-related adverse events