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Regulatory B cell repertoire defects predispose lung cancer patients to immune-related toxicity following checkpoint blockade. | LitMetric

AI Article Synopsis

  • Pembrolizumab, a checkpoint blocker, shows effective long-term responses in advanced non-small cell lung cancer but can lead to serious immune-related adverse events (irAEs) in some patients.
  • The study highlights a deficiency in regulatory B cells, specifically those producing IL-10, which fails to control overly reactive T cell activity when PD-1/PD-L1 is inhibited, resulting in severe auto-inflammatory effects.
  • The research suggests that profiling B cells before treatment could help identify lung cancer patients who are at a higher risk of experiencing severe irAEs during checkpoint blockade therapy.

Article Abstract

Checkpoint blockade with Pembrolizumab, has demonstrated durable clinical responses in advanced non-small cell lung cancer, however, treatment is offset by the development of high-grade immune related adverse events (irAEs) in some patients. Here, we show that in these patients a deficient Breg checkpoint fails to limit self-reactive T cell enhanced activity and auto-antibody formation enabled by PD-1/PD-L1 blockade, leading to severe auto-inflammatory sequelae. Principally a failure of IL-10 producing regulatory B cells as demonstrated through functional ex vivo assays and deep phenotyping mass cytometric analysis, is a major and significant finding in patients who develop high-grade irAEs when undergoing treatment with anti-PD1/PD-L1 checkpoint blockade. There is currently a lack of biomarkers to identify a priori those patients at greatest risk of developing severe auto-inflammatory syndrome. Pre-therapy B cell profiling could provide an important tool to identify lung cancer patients at high risk of developing severe irAEs on checkpoint blockade.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174492PMC
http://dx.doi.org/10.1038/s41467-022-30863-xDOI Listing

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