Loading
Life sciences · Journal article
Cancer Immunology Immunotherapy · November 6, 2026
No summary has been generated for this record yet. What follows is drawn from its source metadata only.
Journal article.
No findings were extractable from the material analysed.
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
The source did not state who this applies to in practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
This record has not been graded across any dimension yet. Treat the label above as provisional and read the source.
What is missing. This record has no bottom line, key findings, reported figures, evidence dimensions. That is a gap in the analysis, not a judgement about the study.
Abstract Immune checkpoint inhibitors (ICI) targeting CTLA-4 and PD-1 improve cancer outcomes but are frequently associated with breakdown of peripheral tolerance, triggering immune-related adverse events (irAEs). While T-cell mediated mechanisms have been extensively studied, the contribution of B cells in irAE pathogenesis remains underexplored. Here, we performed comprehensive phenotypic, functional, and signaling analyses of peripheral B cells in two independent ICI-treated patient cohorts: a melanoma cohort (PREDIMEL) and a pan-cancer cohort (AMICI). Before treatment initiation, patients who subsequently developed irAEs displayed enrichment of highly activated and differentiated B-cell subsets, including IgD⁻ memory B cells, activated memory B cells, and plasmablasts depending on cancer type. Beyond these phenotypic alterations, B cells from irAE-prone melanoma patients exhibited intrinsic functional dysregulation, characterized by enhanced BCR-induced signaling through Syk and PLCγ2 phosphorylation and increased antibody secretion upon stimulation. Despite inter-tumor and inter-cohort heterogeneity, irAE-associated B-cell subsets shared a common signature of increased activation and reduced inhibitory receptor expression. Together, these findings identify a pre-existing B-cell state with heightened activation potential and impaired regulation, revealing a functional B-cell predisposition that may contribute to immune toxicity following ICI therapy.