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The Journal of Clinical Investigation reports results of a study showing that increases in CD21lo B cells and plasmablasts following that combination checkpoint blockade (CCB) preceded the onset of immune-related adverse events (IRAEs).
While some have postulated that IRAEs are thought to be T cell mediated, B cells have also been implicated. Investigators studied 39 melanoma patients undergoing treatment with either anti-CTLA4 or anti-PD1, or combination CCB therapy. They analyzed changes in circulating B cells before and after the first cycle of therapy of immune checkpoint blockade (23 received combination therapy, 8 received anti-CTLA4, and 8 received anti-PD1).
The first cycle of therapy was associated with a decline in circulating B cells and an increase in CD21lo B cells and plasmablasts. PD1 expression was higher in the CD21lo B cells, and B cell receptor sequencing of these cells demonstrated greater clonality and a higher frequency of clones compared with CD21hi cells.
CCB induced proliferation in the CD21lo compartment, and single-cell RNA sequencing identified B cell activation in cells with genomic profiles of CD21lo B cells in vivo.
Treatment-induced changes in B cells preceded and correlated with both the frequency and timing of IRAEs. Patients with early B cell changes experienced higher rates of grade 3 or higher IRAEs 6 months after CCB.
Thus, early changes in B cells following CCB may identify patients who are at increased risk of IRAEs, and preemptive strategies targeting B cells may reduce toxicities in these patients.
An accompanying editorial discusses the possibility of these B cell changes as predictive biomarkers for high-grade IRAEs that may be useful in patient monitoring or guiding treatment strategies to prevent IRAEs. (https://buff.ly/2mpzGRN)