AI Article Synopsis

  • Immune checkpoint blockers (ICBs) can activate CD8 T cells, leading to both positive anti-cancer effects and adverse immune-related events (irAEs), but their link to overall clinical outcomes is not well understood.* -
  • A study examined the connection between irAE development and patient survival in metastatic melanoma by analyzing data from two groups of patients receiving different ICB treatments and assessing gene expression in CD8 T cells.* -
  • Results showed that over half of the patients experienced early irAEs, which correlated with longer progression-free and overall survival, indicating that irAEs might reflect baseline immune activation and influence treatment outcomes.*

Article Abstract

Background: Immune checkpoint blockers (ICBs) activate CD8 T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.

Methods: Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab-sICB) or combination (nivolumab and ipilimumab-cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8 T cells was sequenced and differential gene expression according to irAE development assessed.

Results: 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9-33.4) versus not-reached (P = 2.8 × 10). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8 T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.

Conclusions: Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110747PMC
http://dx.doi.org/10.1038/s41416-021-01310-3DOI Listing

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