Combination immune checkpoint blockade with anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and anti-programmed cell death protein 1 (PD1) leads to higher response rates in patients with melanoma than either single agent alone. Yet, a drawback of this combination is an increase in immune-related adverse events. Until now attention has focused on T cell-mediated immune responses following immune checkpoint therapy, and the role B cells might play has been relatively unexplored. Das et al. found a decrease in circulating B cells and an increase in CD21lo B cells and plasmablasts following inhibition of CTLA4 and PD1 in patients. The CD21lo B cells were associated with greater clonality, activation and PD1 expression. Importantly, these early B cell changes occurred before and correlated with both the number and timing of treatment-related toxicities. Thus, detection of B cells could serve as a predictive biomarker of patients at increased risk of developing autoimmunity.
References
Das, R. et al. Early B cell changes predict autoimmunity following combination immune checkpoint blockade. J. Clin. Invest. http://dx.doi.org/10.1172/JCI96798 (2018)
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Dart, A. Bad B cells. Nat Rev Cancer 18, 66 (2018). https://doi.org/10.1038/nrc.2018.7
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DOI: https://doi.org/10.1038/nrc.2018.7