Journal: Signal Transduction and Targeted Therapy
Article Title: Single-cell imaging analysis, therapeutic modeling and a Phase Ib trial validate BCL-2 as a target across heterogeneous castration-resistant prostate cancer
doi: 10.1038/s41392-026-02700-w
Figure Lengend Snippet: Vectra and IMC analysis reveals castration-induced dynamic changes in AR +/- BCL-2 +/- cell types in 4 xenograft CRPC models. a – d tSNE plots of IMC-derived single-cell imaging data. Shown are the individual and merged tSNE plots from LNCaP-AD/AI ( a ), LAPC9-AD/AI ( b ), LAPC4-AD/AI ( c ), and VCaP-AD/AI ( d ) xenografts. Columns represent merged AD and AI cell clusters (first column), individual AD and AI cell populations and contours (second and third columns), and AR and BCL-2 expression overlaid on tSNE maps (fourth and fifth columns). Blue and red contours indicate AD and AI cell subpopulations, respectively. e LAPC4-AD tumors are populated mostly by AR + BCL-2 - PCa cells. Shown on top are qmIF WM images (scale bar, 800 μm) and at the bottom zoom-in images (scale bar, 80 μm for all panels). f LAPC4-AI (1° CRPC) tumors are populated by AR cyto BCL-2 + PCa cells. Shown on top are qmIF WM images (scale bar, 800 μm) and at the bottom zoom-in images illustrating cytoplasmic AR + LAPC4-AI cells with upregulated BCL-2 (scale bar, 80 μm for all panels). g IMC images of AR and BCL-2 in LAPC4-AD and LAPC4-AI tumors (scale bar, 200 μm) with representative zoom-in images of AR and BCL-2 shown below (scale bar, 100 μm for all panels)
Article Snippet: To confirm and extend these findings, we employed Vectra-based quantitative multiplex immunofluorescence (qmIF) to assess PCa cells expressing BCL-2 and/or AR in regular FFPE (formalin-fixed and paraffin-embedded) sections as well as TMA (tissue microarray) and whole-mount (WM) sections from benign prostate ( n = 123), treatment-naïve primary PCa ( n = 125) and treatment-failed CRPC ( n = 25) (Fig. ; supplementary Figs. – , supplementary Table ).
Techniques: Derivative Assay, Single Cell, Imaging, Expressing