Tertiary lymphoid structures (TLSs) are associated with improved cancer immunotherapy responses. However, TLSs vary in their ability to elicit anticancer immune activity, so it is important to develop databases that allow study of variables that regulate their function. We applied single RNA molecule resolution imaging to longitudinal biopsies taken from women with TLS-enriched triple negative breast cancers prior to therapy, after pembrolizumab and after pembrolizumab plus radiation therapy. We developed a comput…

Abstract Phenotypic plasticity is a recognized mechanism of therapeutic resistance in prostate cancer (PCa), however current knowledge of driver mechanisms and therapeutic interventions are limited. Using genetically engineered mouse models (GEMMs) devoid of Pten and Rb1, we previously demonstrated the chromatin reprogramming factor enhancer of zeste homolog 2 (EZH2) as an important regulator of alternative transcription programs promoting phenotypic plasticity. Here, using a multi-omics approach we demonstrate th…

Summary Cancer immunotherapy trials have had variable success, prompting a search for biomarkers of response. Tertiary lymphoid structures (TLS) have emerged as prognostic for multiple tumor types. These ectopic immunological bodies resemble secondary lymphoid organs with segregated B and T cell zones, but they are heterogeneous in their organization and cellular composition. These features have consequences in terms of prognostication and disease clearance, so there is interest in what drives TLS heterogeneity an…

Abstract Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods 1 . Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously unde…

High-resolution spatial transcriptomics enables mapping of RNA expression directly from intact tissue sections; however, its utility for the elucidation of disease processes and therapeutically actionable pathways remains unexplored. We applied Slide-seqV2 to mouse and human kidneys, in healthy and distinct disease paradigms. First, we established the feasibility of Slide-seqV2 in tissue from nine distinct human kidneys, which revealed a cell neighborhood centered around a population of <i>LYVE1+</i> macrophages. …