Journal: Frontiers in Immunology
Article Title: CheckDyn: a multi-cohort computational framework for profiling treatment-induced immune checkpoint dynamics and predicting adaptive resistance to immune checkpoint blockade
doi: 10.3389/fimmu.2026.1847297
Figure Lengend Snippet: Study overview: multi-cohort paired transcriptomics of checkpoint dynamics. (a) Study design schematic. Paired tumor biopsies were collected before and after ICB therapy (anti-PD-1 or anti-PD-1/anti-CTLA-4), and transcriptomic profiles were used for checkpoint dynamics analysis and clinical response association. (b) Dataset overview. Bar chart showing the number of paired patients (pre + post biopsies) per cohort and cancer type. n = 42 from GSE91061 (melanoma), n = 11 from Sade-Feldman2018/ GSE120575 (melanoma), n = 11 from Yost2019/ GSE123813 (BCC); total n = 64. (c) Meta-analysis mean fold-change (Z-score) per checkpoint gene across all datasets. Asterisks indicate genes reaching padj < 0.05. Genes are colored by functional category: inhibitory checkpoints (red), co-stimulatory molecules (teal), metabolic checkpoints (salmon), exhaustion markers (blue-grey). (d) Six-step analysis pipeline: data collection (4 cohorts, n = 64 paired) → pseudo-bulk aggregation and Z-score batch correction → paired DE analysis (Stouffer Z meta-analysis) → network rewiring (co-expression, hub shift) → ensemble model (AUC = 0.812, n = 38 genes) → clinical implication (combination therapy).
Article Snippet: We integrated publicly available RNA-seq and scRNA-seq data from 64 paired tumor samples spanning melanoma, basal cell carcinoma, and non-small-cell lung cancer ( GSE91061 , GSE120575 , GSE123813 , GSE176021 ), applying pseudo-bulk aggregation, Z-score batch correction, and Stouffer meta-analysis for cross-cohort harmonization.
Techniques: Transcriptomics, Functional Assay, Expressing