Pathology

Spatial multi-omics defines PDAC classical–basal spectrum and microenvironmental niches

Multi-modal spatial and single-cell transcriptomics of 39 untreated PDACs show a continuous classical-to-basal tumor spectrum within every patient. Each subtype associates with distinct stromal neighborhoods, extracellular matrix patterns, and immunosuppressive, therapy-resistance programs. The study highlights mixed KRAS mutation subclones and tertiary lymphoid structures, with biomarkers distinguishing these from lymph nodes. Findings clarify which PDAC features are captured by bulk data and model systems, guiding interpretation of research and potential biomarkers. 1

Neutrophil phenotypes and niches structure the CRC immune microenvironment

An atlas of over 4 million single cells from 1,670 colorectal cancers classifies tumors into immune desert, B-cell, T-cell, or myeloid-enriched phenotypes. Within myeloid cells, four consensus immunomodulatory programs and a neutrophil subset with antigen-presenting features are defined. Patient-derived organoids demonstrate KRAS-dependent pro-tumorigenic polarization of neutrophils, linking genotype to myeloid behavior. Spatial multimodal profiling reveals IL-1–driven neutrophil–fibroblast niches and shows cancer-derived signals reprogram neutrophil production in bone marrow. 2

Whole-transcriptome sequencing as a routine FFPE fusion assay with strict QC

Whole-transcriptome sequencing was implemented as a diagnostic fusion assay and benchmarked against Archer FusionPlex and TSO500 RNA on FFPE tumors. Defined QC requirements included tumor cell content ≥40%, ≥50 ng RNA input, ≥50 million reads, and median insert size >100 bp. In an initial cohort, WTS detected 92% of known fusions, and in 357 validation samples it matched panel assays when QC was met. Deployed across 812 clinical cases, WTS detected 121 fusions and also uncovered novel fusions, pathogens, and oncogenic pathway signatures. About one-third of samples required fallback to targeted assays due to low tumor cell content, underscoring pre-analytic triage needs. 3

Benchmarking Visium, Xenium, CosMx and derivatives on FFPE cancers

Five commercial spatial transcriptomics platforms were systematically compared on matched FFPE sections from six human cancer types. Sequencing-based and imaging-based systems showed differing strengths in transcript and UMI recovery, cell-type resolution, and histology concordance. Sampling strategy and tissue area coverage produced trade-offs between spatial resolution and preservation of broader architectural context. Comparison of Xenium Multi-Tissue and Xenium Prime revealed substantial differences in transcript recovery and spatial signal despite shared chemistry. Integrated RNA and targeted protein profiling exposed widespread RNA–protein decoupling and spatial heterogeneity, informing assay interpretation. 4