B cells as biomarkers: predicting immune checkpoint therapy adverse events
Shannon M. Liudahl, Lisa M. Coussens
Shannon M. Liudahl, Lisa M. Coussens
Published January 8, 2018
Citation Information: J Clin Invest. 2018;128(2):577-579. https://doi.org/10.1172/JCI99036.
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Commentary

B cells as biomarkers: predicting immune checkpoint therapy adverse events

Abstract

Immune checkpoint inhibitors are becoming a cornerstone of cancer immunotherapy as a result of their clinical success in relieving immune suppression and driving durable antitumor T cell responses in certain subsets of patients. Unfortunately, checkpoint inhibition is also associated with treatment-related toxicities that result in a myriad of side effects, ranging from mild and manageable to severe and debilitating. In this issue of the JCI, Das and colleagues report an association between early therapy-induced changes in circulating B cells and an increased risk of high-grade immune-related adverse events (IRAEs) in patients treated with checkpoint inhibitors that target cytotoxic T lymphocyte–associated antigen-4 (CTLA4) and programmed cell death protein 1 (PD1). These findings identify potential predictive biomarkers for high-grade IRAEs that may be leveraged to improve patient monitoring and may prompt new treatment strategies to prevent IRAEs.

Authors

Shannon M. Liudahl, Lisa M. Coussens

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Figure 1

Changes in circulating B cells predict IRAE risk in patients receiving combined anti-CTLA4 and anti-PD1 therapy.

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Changes in circulating B cells predict IRAE risk in patients receiving c...
Patients showing changes in circulating B cells after one cycle of combination anti-CTLA4 and anti-PD1 therapy (compared with their pretreatment baseline) have an increased risk of developing high-grade IRAEs. Specifically, a post-treatment reduction in total peripheral B cells and a coincident enrichment of differentiated CD21lo PD1+ memory B cells and plasmablasts correlate with subsequent IRAE development. B cell changes are a unique immune biomarker of IRAE risk, as early changes in the frequency of other circulating leukocyte populations were not detected after therapy (data not shown). Select high-grade IRAE pathologies associated with combined anti-CTLA4 and anti-PD1 mAb therapy are depicted, and patients who showed B cell changes had a median three-week time to onset of one or more such IRAEs.