Abstract 4959: Trekker enables high-sensitivity, single-cell spatial profiling of the FFPE lung SCC tumor microenvironment without segmentation or deconvolution

Abstract Squamous cell carcinoma (SCC) is a highly heterogeneous malignancy characterized by complex cellular architecture, variable patterns of immune infiltration, and diverse stromal interactions that influence progression, metastatic potential, and therapeutic response. A detailed understanding of the SCC tumor microenvironment (TME) is therefore essential for identifying biomarkers, resolving resistant niches, and guiding precision oncology strategies. Although single-cell sequencing captures cellular diversity, it lacks spatial context, while most spatial transcriptomics platforms depend on complex protocols, proprietary reagents, and computationally intensive segmentation, deconvolution, or binning steps that limit true single-cell resolution—especially in FFPE clinical samples. To address these challenges, we present Trekker, a flexible, next-generation single-cell spatial transcriptomics platform that delivers spatial context with the simplicity of standard snRNA-seq. Using a Slide-tag-inspired spatial tagging approach ( Russel et al., 2023), Trekker™ indexes nuclei directly within intact tissue sections and is compatible with same-section H Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4959.