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Anti-VEGF treatment potentiates ICB responses through a BAFF and IL-12-dependent reprogramming of the TME

GSE284205 Homo sapiens Expression profiling by high throughput sequencing 7 samples Submitted 2025/03/16 Platform GPL24676
Summary
Anti-VEGF treatment has shown clinical activity in combination with checkpoint inhibitor therapy, but the exact mechanism is not known. We show that adding VEGF blockade to the ICB combination of anti-CTLA4 + anti-PD-L1 in cholangiocarcinoma unleashed a therapeutic efficacy driven through a novel multimodal mechanism dependent on BAFF production by T and myeloid cells, leading to a BAFF-dependent proinflammatory B cell response characterized by Germinal center B cell and plasma cell expansion, as well as IL-12 production. Using single cell RNA sequencing (scRNA-Seq) of paired pre- and post-treatment tumor biopsy samples from patients treated with anti-CTLA4, anti-PD-L1 and anti-VEGF, we characterized the treatment-associated immunological changes.
Published in
Anti-vascular endothelial growth factor treatment potentiates immune checkpoint blockade through a BAFF- and IL-12-dependent reprogramming of the TME
Benmebarek MR, Oguz C, Seifert M et al. · Immunity 2025 · PMID 40088889 · doi:10.1016/j.immuni.2025.02.017
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Also filed as BioProject PRJNA1197972 and SRA study SRP551276. Searching any of these in the dataset finder brings you back here.

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