Anti-PD-1-induced high-grade hepatitis associated with corticosteroid-resistant T cells: a case report

We present an unusually severe case arising in a melanoma patient after more than 6  months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control. Mass cytometry allowed comprehensive phenotyping of circulating lymphocytes and revealed that CD4+ T cells were profoundly depleted by ATG, while CD8+ T cells, B cells, NK cells and monocytes were relatively spared. Multiple abnormalities in CD4+ T cell phenotype were stably present in the patient before disease onset. These included a population of CCR4−CCR6− effector/memory CD4+ T cells expressing intermediate levels of the Th1-related chemokine receptor CXCR3 and abnormally high multi-drug resistance type 1 transporter (MDR1) activity as assessed by a rhodamine 123 excretion assay. Expression of MDR1 has been implicated in steroid resistance and may have contributed to the severity and lack of a sustained steroid response in this patient. The number of CD4+ rhodamine 123-excreting cells was reduced  >  3.5-fold after steroid and ATG treatment. This case illustrates the need to consider this form of steroid resistance in patients failing treatment with corticosteroids. It also highlights the need for both better identification of patients at risk and the development of treatments that involve mo re specific immune suppression.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
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Source: Advances in Dermatology and Allergology - Category: Dermatology Tags: Postepy Dermatol Alergol Source Type: research
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Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
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Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
This article is protected by copyright. All rights reserved. PMID: 31002181 [PubMed - as supplied by publisher]
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: Clin Exp Pharmacol Physiol Source Type: research
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Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
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Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
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