Biology subjects

Kwong, L. N.

Publications and source records attributed to Kwong, L. N..

2 recordsLinked to original sources

bioRxiv2026

A modular generalist-specialist AI framework for ROI selection across spatial profiling workflow

Selection of regions of interest (ROIs) is often a crucial step in spatial molecular profiling and many pathology tasks, with substantial implications for research reproducibility and biological interpretability. To provide a reproducible and adaptive framework for AI-guided ROI selection, we developed a modular generalist-specialist solution across spatial profiling platforms. In a cohort comprising 55 tumor types from 160 tissue donors profiled using NanoString Digital Spatial Profiling and multiplex immunofluorescence, we first established a protein-profiling reference atlas capturing compartment-specific immune, checkpoint, stromal, and proliferation patterns. We then developed an AI Specialist Task-Oriented Model for ROI Selection (ASTROS) and tested comprehensive benchmarks considering specialist-only (ASTROS), generalist-only (PLIP/GFM), and hybrid generalist-specialist strategies, showing that the latter provides a balanced tradeoff across slide-level signal preservation, pathologist-reference concordance, within-slide placement consistency, and large-slide computational efficiency. We further demonstrated the feasibility of virtual staining for ROI preview and modular ROI placement for other spatial omics technologies, Visium and Visium HD workflows. Together, these results support our proposed framework to enable ROI selection responding to unmet needs for reducing inter-rater variability, reproducibility, and versatility in spatial profiling experiments.

pathology↗

bioRxiv2022

Microparticle-delivered Cxcl9 delays the relapse of Braf inhibitor-treated melanoma

Patients with BRAF-mutant melanoma show significant responses to combined BRAF and MEK inhibition, but most relapse within 2 years. A major reservoir for drug resistance is minimal residual disease (MRD), comprised of drug-tolerant tumor cells laying in a dormant state. Towards exploiting potential therapeutic vulnerabilities of MRD, we established a genetically engineered mouse model of BrafV600E-driven melanoma MRD wherein genetic BrafV600E extinction leads to strong but incomplete tumor regression. Transcriptional time-course analysis after BrafV600E extinction revealed that after an initial surge of immune activation, tumors later became immunologically "cold" after MRD establishment. Computational analysis identified candidate T-cell recruiting chemokines that may be central players in the process, being strongly upregulated initially and steeply decreasing as the immune response faded. Therefore, we hypothesized that sustaining the chemokine signaling could impair MRD maintenance through increased recruitment of effector T-cells. We show that intratumoral administration of recombinant Cxcl9, either naked or loaded in microparticles, significantly impaired MRD relapse in BRAF-inhibited tumors, including several complete responses after microparticle-delivered rCxcl9 combined with BRAF and MEK-inhibition. Our experiments constitute a proof of concept that chemokine-based microparticle delivery systems are a potential strategy to forestall tumor relapse and thus improve the clinical success of frontline treatment methods.

cancer biology↗