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PD-L1 expressing granulomatous reaction as an on-target mechanism of steroid-refractory immune hepatotoxicity

Black, JR; Goldin, RD; Foxton, M; Marafioti, T; Akarca, AU; Pria, AD; Brock, C; ... Pinato, DJ; + view all (2019) PD-L1 expressing granulomatous reaction as an on-target mechanism of steroid-refractory immune hepatotoxicity. Immunotherapy , 11 (7) pp. 585-590. 10.2217/imt-2018-0187.

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Abstract

Immune-related hepatitis is an important toxicity from immune-checkpoint inhibitor therapy, affecting up to 20% of patients on dual cytotoxic T-lymphocyte antigen 4/programmed cell death 1 (CTLA-4/PD-1) inhibitors. The mechanisms underlying this type of drug-induced liver injury are poorly understood. We report the case of a patient with immune-checkpoint inhibitor-related hepatitis where the presence of a diffuse granulomatous, PD-L1-positive infiltrate on liver biopsy correlated with poor response to corticosteroids. Our findings suggest a potential role for activation of the PD-1 pathway within the histiocitic infiltrate as a mechanism of toxicity. Further studies should address the role of macrophages in this patient group characterized by steroid-refractoriness.

Type: Article
Title: PD-L1 expressing granulomatous reaction as an on-target mechanism of steroid-refractory immune hepatotoxicity
Location: England
DOI: 10.2217/imt-2018-0187
Publisher version: https://doi.org/10.2217/imt-2018-0187
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: DILI, hepatitis, hepatotoxicity, immune checkpoint inhibitors, toxicity
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
URI: https://discovery.ucl.ac.uk/id/eprint/10075089
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