Biology subjects

Ben-uri, R.

Publications and source records attributed to Ben-uri, R..

3 recordsLinked to original sources

bioRxiv2026

Spatially enforced engagement of PD-1⁺ T cells with AXL⁺ cells reprograms the tumor microenvironment and overcomes anti-PD-1 resistance

Background: AXL overexpression promotes tumor-cell plasticity, local immune suppression, and resistance to PD-1 blockade. Conventional anti-AXL and anti-PD-1 antibodies combinations act independently and do not ensure physical proximity between PD-1+ T cells and AXL+ cells within the immunosuppressive tumor microenvironment. Methods: To address this limitation, we developed a non-tandem, tetravalent IgG bispecific antibody designed to simultaneously engage PD-1 and AXL (BiTE-AXL/PD-1). Its antitumor activity was evaluated using in vitro functional assays and humanized and immunocompetent head and neck squamous cell carcinoma (HNSCC) models and compared with the combination of monospecific anti-AXL and anti-PD-1 antibodies. Spatial multiplex imaging was used to characterize treatment-associated changes in the tumor microenvironment of an anti-PD-1-resistant murine model. Results: BiTE-AXL/PD-1 enhanced T-cell activation, promoted AXL-dependent tumor-T-cell conjugation, and increased tumor-cell killing in vitro, outperforming the combination of the two monospecific antibodies. In humanized and immunocompetent HNSCC models, BiTE treatment significantly delayed tumor growth compared with the antibody combination and was well tolerated, with no overt toxicity. Spatial multiplex imaging revealed a shift from a fibroblast-dominated microenvironment characterized by exhausted CD8+ T cells toward dendritic-cell- and CD8+ T-cell-enriched niches associated with antitumor immune activity. Conclusion: BiTE-AXL/PD-1 promotes physical proximity between PD-1+ T cells and AXL+ cells, enhances antitumor immune responses, and remodels the immunosuppressive tumor microenvironment. These findings support PD-1/AXL bispecific targeting as a promising therapeutic strategy to overcome resistance to PD-1 blockade in HNSCC.

cancer biology↗

bioRxiv2026

Single-section multiplexed imaging enables comprehensive lung cancer diagnosis

Accurate and timely diagnosis is essential for effective lung cancer treatment. However, contemporary workflows rely on sequential immunohistochemistry of small biopsy specimens, which can exhaust tissue, limit biomarker assessment, and delay treatment decisions. Here, we demonstrate that multiplexed imaging addresses these limitations by enabling comprehensive lung cancer diagnosis from a single tissue section. We developed and validated a clinically informed multiplexed antibody panel that integrates tumor classification, predictive biomarker assessment, and immune profiling. In diagnostic biopsies, multiplexed imaging achieved 96% concordance with standard pathology, while enabling accurate automated PD-L1 scoring and rapid detection of clinically approved and emerging actionable targets. Simultaneously measuring dozens of proteins improves standard pathology by incorporating complex multi-protein biomarkers, supporting quantitative computational analysis to streamline diagnosis, and generating spatial data for translational research. By reducing turnaround time and preserving scarce tissue, this workflow has the potential to accelerate treatment decisions, improve patient outcomes and bridge clinical care with translational discovery.

cancer biology↗

bioRxiv2025

CellTune: An integrative software for accurate cell classification in spatial proteomics

Spatial proteomics measures multiple proteins in situ, capturing tissue complexity. However, cell classification in densely packed tissues remains challenging due to the lack of efficient classification algorithms, annotation tools, and high-quality labeled datasets to benchmark computational methods. We introduce CellTune, an integrated software for analysis of large spatial proteomics datasets, which streamlines precise cell classification through an optimized human-in-the-loop active learning workflow. It advances core capabilities across within a unified, intuitive, and code-free interface. To evaluate CellTune, we created CellTuneDepot, a resource of 40k manually-annotated cells and 3.5 million high-quality labeled cells across 60 cell types. CellTune outperforms alternative methods, achieving accuracy comparable to human performance while enabling increased classification resolution and discovery of novel cell types. Together, CellTune and CellTuneDepot provide researchers with a tool for state-of-the-art classification accuracy and resolution at scale to drive biological insights.

bioinformatics↗