Biology subjects

Verghese, G.

Publications and source records attributed to Verghese, G..

3 recordsLinked to original sources

bioRxiv2026

Extrafollicular plasma cells disable dendritic cell-T-cell priming in tumor-draining lymph nodes

How plasma cells (PCs) shape anti-tumor immunity is unclear. We hypothesized that conflicting prognostic associations reflect differences in immune context and PC ontogeny. We identify extrafollicular (EF)-PCs as an antibody-independent checkpoint that aborts priming by disabling the cDC1[->]CD8+ T-cell axis in tumor-draining lymph nodes (td-LNs). EF-PCs blunt cDC1 activation and CCR7-guided repositioning into T-cell zones, precluding formation of TCF1 stem-like CD8 T-cells. Depleting EF-PCs in vivo restores cDC1 trafficking, expands the stem-like reservoir, increases intratumoral CD8 infiltration, and restrains tumor growth; benefit is lost with CD8 T-cell ablation. Neither serum transfer nor Fc{gamma} receptor blockade reverses tumor control, supporting a non-canonical, antibody-independent mechanism. Across independent triple-negative breast cancer cohorts, we find EF-PC hyperplasia in td-LNs and tumors; and within immune-cold cases, EF-PC burden stratifies poor prognosis and metastatic risk. A cross-species EF-PC signature maps to a conserved PC-state across cancer types that is linked to poor outcome and immune-checkpoint blockade resistance. EF-PCs thus relocate the dominant failure point to td-LNs and offer a tractable upstream target to convert immune-cold tumors into immune-responsive disease.

immunology↗

bioRxiv2025

SMART: A Spatio-Molecular Atlas of Response Trajectories in Triple-Negative Breast Cancer

A major challenge in treating Triple-Negative Breast Cancer (TNBC) lies in its molecular, morphological and clinical heterogeneity, which hampers accurate prediction of responses to neoadjuvant treatment. To address this, we introduce SMART: Spatio-Molecular Atlas of Response Trajectories, a comprehensive, multimodal resource compiled from 129 TNBC samples across 89 patients, obtained before, during, and after neoadjuvant chemotherapy (NACT). SMART comprises of 5,096 high quality manually selected spatial transcriptomic profiles enriched for epithelial, immune, or stromal compartments; paralleled with histological annotations, imagebased network analysis and protein expression. Seven novel spatial epithelial archetypes (EAs), seven tumour-immune microenvironments (TIMEs) and their co-localisation patterns were defined, revealing an opposing prevalence of functionally divergent EAs between response groups and the prognostic significance of B-cell enriched TIMEs, in particular those surrounding histologically normal epithelium adjacent to the tumour. The SMART dataset and analytical tools are publicly available via the PharosAI platform, providing the research community with the most comprehensive, manually annotated spatio-molecular transcriptomics atlas of NACT-treated TNBC to date.

cancer biology↗

bioRxiv2025

Normal breast tissue classifiers assess large-scale tissue compartments with high accuracy

Cancer research emphasises early detection, yet quantitative methods for normal tissue analysis remain limited. Digitised haematoxylin and eosin (H&E)-stained slides enable computational histopathology, but artificial intelligence (AI)-based analysis of normal breast tissue (NBT) in whole slide images (WSIs) remains scarce. We curated 70 WSIs of NBTs from multiple sources and cohorts with pathologist-guided manual annotations of epithelium, stroma, and adipocytes (https://github.com/cancerbioinformatics/OASIS). We developed robust convolutional neural network (CNN)-based, patch-level classification models, named NBT-Classifiers, to tessellate and classify NBTs at different scales. Across three external cohorts, NBT-Classifiers trained on 128{square}x{square}128{square}{micro}m and 256{square}x{square}256{square}{micro}m patches achieved AUCs of 0.98-1.00. The model learned independent normal features different from those of precancerous and cancerous epithelium, which were further visualised using two explainable AI techniques. When integrated into an end-to-end preprocessing pipeline, NBT-Classifiers facilitate efficient downstream analysis within peri-lobular regions. NBT-Classifiers provide robust compartment-specific analytical tools and enhance our understanding of NBT appearances, which serve as valuable reference points for identifying premalignant changes and guiding early breast cancer prevention strategies.

pathology↗