Prediction of immune checkpoint blockade‐related hepatitis in metastatic melanoma patients

Summary The introduction of clinical antibodies against programmed death‐1 (PD‐1) and cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) has revolutionized cancer treatment. Immune checkpoint blockade has enormous therapeutic potential and is widely prescribed for treating various cancers. However...

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Bibliographic Details
Published in:Journal der Deutschen Dermatologischen Gesellschaft 2022-06, Vol.20 (6), p.773-775
Main Authors: Schilling, Hannah‐Lou, Hutchinson, James A., Haferkamp, Sebastian
Format: Article
Language:English
Subjects:
Adverse events
Apoptosis
CD4 antigen
Chronic infection
Cytomegalovirus
Cytotoxicity
Effector cells
Etiology
Hepatitis
Immune checkpoint
Immunological memory
Lymphocytes T
Melanoma
Memory cells
Metastases
Patients
Recurrent infection
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Summary:Summary The introduction of clinical antibodies against programmed death‐1 (PD‐1) and cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) has revolutionized cancer treatment. Immune checkpoint blockade has enormous therapeutic potential and is widely prescribed for treating various cancers. However, immune‐related adverse events in checkpoint blockade‐treated patients are common and limit its clinical application. Despite efforts to understand the etiology of immune‐related adverse events, the underlying cellular reactions remain elusive. Recently, our group identified a subset of patients with metastatic melanoma that are predisposed to hepatitis after combined PD‐1 and CTLA‐4 blockade. These patients are characterized by pre‐treatment expansion of effector memory CD4+ T cells (TEM cells) in blood. We attributed this expansion to chronic or recurrent subclinical immune responses against cytomegalovirus (CMV) infection. Accordingly, baseline expansion of TEM cells is a reliable biomarker of hepatitis risk that identifies a subgroup of patients who might benefit from prophylactic CMV treatment with valganciclovir.
ISSN:1610-0379
1610-0387
DOI:10.1111/ddg.14726