Single-cell and spatial genomic landscape of non-small cell lung cancer brain metastases

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Language: Английский

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Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma

Science Immunology, Journal Year: 2025, Volume and Issue: 10(104)

Published: Feb. 7, 2025

The bone marrow microenvironment plays a crucial role in the development of multiple myeloma. As disease progresses, malignant myeloma cells can evolve to survive outside marrow. However, processes underlying independence and their consequences for immune control remain poorly understood. Here, we conducted single-cell spatial multiomics analyses marrow-confined intramedullary paired breakout lesions that disrupt cortical bone. These revealed distinct cellular architectural features lesions, characterized by extensive areas plasma interspersed with lesion-specific solitary natural killer macrophage populations, as well focal accumulations cell agglomerates. Within these agglomerates, spatially confined T clones expanded alongside various cells, coinciding local genomic evolution tumor cells. identify hotspot tumor-immune interactions diversification, representing key event pathogenesis.

Language: Английский

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Tribus: Semi-automated discovery of cell identities and phenotypes from multiplexed imaging and proteomic data

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 14, 2024

Abstract Motivation Multiplexed imaging and single-cell analysis are increasingly applied to investigate the tissue spatial ecosystems in cancer other complex diseases. Accurate phenotyping based on marker combinations is a critical but challenging task due (i) low reproducibility across experiments with manual thresholding, and, (ii) labor-intensive ground-truth expert annotation required for learning-based methods. Results We developed Tribus, an interactive knowledge-based classifier multiplexed images proteomic datasets that avoids hard-set thresholds labeling. demonstrated Tribus recovers fine-grained cell types, matching gold standard annotations by human experts. Additionally, can target ambiguous populations discover phenotypically distinct subtypes. Through benchmarking against three similar methods four public ground truth labels, we show outperforms accuracy computational efficiency, reducing runtime order of magnitude. Finally, demonstrate performance rapid precise two large in-house whole-slide datasets. Availability available at https://github.com/farkkilab/tribus as open-source Python package.

Language: Английский

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Spatial analysis by current multiplexed imaging technologies for the molecular characterisation of cancer tissues

British Journal of Cancer, Journal Year: 2024, Volume and Issue: 131(11), P. 1737 - 1747

Published: Oct. 22, 2024

Tumours are composed of tumour cells and the surrounding microenvironment (TME), molecular characterisation various elements TME their interactions is essential for elucidating mechanisms progression developing better therapeutic strategies. Multiplex imaging a technique that can quantify expression multiple protein markers on same tissue section while maintaining spatial positioning, this method has been rapidly developed in cancer research recent years. Many multiplex technologies analysis methods emerging, elucidation principles features essential. In review, we provide an overview latest techniques by type staining introduction to image methods, primarily focusing cellular properties, providing deeper insight into organisation biology TME.

Language: Английский

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Multiomic analysis identifies suppressive myeloid cell populations in human TB granulomas.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Tuberculosis (TB) remains a major global health challenge, particularly in the context of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb). Host-directed therapies (HDTs) have been proposed as adjunctive therapy to enhance immune control infection. Recently, one such HDT, pharmacologic modulation myeloid-derived suppressor cells (MDSCs), has treat MDR-TB. While MDSCs well characterized cancer, their role TB pathogenesis unclear. To investigate whether or other myeloid populations contribute granuloma microenvironments (GME), we performed spatial transcriptional profiling and single-cell immunophenotyping on eighty-four granulomas lung specimens from three individuals with active disease. Granulomas were histologically classified based H&E staining, signatures compared across regions interest (ROIs) at different states maturation. Our analysis revealed that suppression within was not primarily driven by classical but rather multiple cell subsets, including dendritic expressing indoleamine 2,3 dioxygenase-1 (IDO1+ DCs). IDO1+ DCs most frequently observed suppressive cells, cellular regions, proximity activated T suggested localized immunosuppression. Importantly, stages contained distinct proportions necrotic showing phenotypes may influence progression. Gene set enrichment (GSEA) further indicated elevated IDO1 expression associated complex response balanced signaling, activation, metabolism. These findings suggest MDSCs, defined tumor microenvironments, likely play minor TB, whereas be key regulators influencing local Mtb infected lung. A deeper understanding is essential assessing potential therapeutic targets treatment.

Language: Английский

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Spatial correlation of the extracellular matrix to immune cell phenotypes in the tumor boundary of ccRCC revealed by cyclic immunohistochemistry

Laboratory Investigation, Journal Year: 2025, Volume and Issue: unknown, P. 104130 - 104130

Published: March 1, 2025

Language: Английский

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Multimodal spatial proteomic profiling in acute myeloid leukemia

npj Precision Oncology, Journal Year: 2025, Volume and Issue: 9(1)

Published: May 20, 2025

Acute myeloid leukemia (AML) resides in an immune-rich microenvironment, yet, immune-based therapies have faltered eliciting durable responses. Bridging this paradox requires a comprehensive understanding of leukemic interactions within the bone marrow microenvironment. We optimized high-throughput tissue-microarray-based pipeline for high-plex spatial immunofluorescence and mass cytometry imaging on single slide, capturing immune, tumor, structural components. Using unbiased clustering K function, we unveiled presence tertiary lymphoid-like aggregates marrow, which validated using transcriptomics independent proteomics approach. then found TLS signatures predictive outcomes AML integrated public 480-patient transcriptomic dataset. By harnessing proteomics, open possibility discovering novel structures that underpin immune response. Further, our study's methodologies resources can be adapted other diseases where decalcification autofluorescence present challenges.

Language: Английский

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Characterization of cancer‐associated fibroblasts and their spatial architecture reveals heterogeneity and survival associations in classic Hodgkin lymphoma

HemaSphere, Journal Year: 2025, Volume and Issue: 9(5)

Published: May 1, 2025

Abstract Cancer‐associated fibroblasts (CAFs) are a heterogeneous population of stromal cells, which modulate the immune system and can have both pro‐ anti‐tumorigenic effects. In classic Hodgkin lymphoma (cHL), role CAFs has remained largely undefined. We applied multiplexed immunofluorescence imaging spatial analysis on tumor samples from two independent cHL patient cohorts ( n = 131 148) to study their interactions with Reed–Sternberg (HRS) microenvironment (TME) cells at single‐cell resolution. show that higher proportions associated favorable outcomes, clinical covariables. contrast, subset CD45 + strong fibroblast‐activation protein positivity, classified as macrophages, was less abundant in nodular sclerosis subtype worse outcomes. Neighborhood allowed for identification colocalization or regional exclusion phenotypically defined cell types recurrent cellular neighborhoods. Despite positive impact CAF survival, patients enrichment platelet‐derived growth factor receptor beta (PDGFRB)‐positive vicinity HRS had survival cohorts, determinants. Our findings distinguish various subsets macrophages impacting underscore importance arrangements TME.

Language: Английский

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CNTools: A computational toolbox for cellular neighborhood analysis from multiplexed images

PLoS Computational Biology, Journal Year: 2024, Volume and Issue: 20(8), P. e1012344 - e1012344

Published: Aug. 28, 2024

Recent studies show that cellular neighborhoods play an important role in evolving biological events such as cancer and diabetes. Therefore, it is critical to accurately efficiently identify from spatially-resolved single-cell transcriptomic data or resolution tissue imaging data. In this work, we develop CNTools, a computational toolbox for end-to-end neighborhood analysis on annotated cell images, comprising both the identification steps. It includes state-of-the-art methods post-identification smoothing techniques, with our newly proposed Cellular Neighbor Embedding (CNE) method Naive Smoothing technique, well several established downstream approaches. We applied CNTools three real-world CODEX datasets evaluated techniques quantitatively qualitatively. shows CNE overall outperformed other revealed more convincing insights. also provided suggestions how choose proper according input

Language: Английский

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Get to know your neighbors with a SNAQ™: A framework for single cell spatial neighborhood analysis in immunohistochemical images

Computational and Structural Biotechnology Journal, Journal Year: 2024, Volume and Issue: 23, P. 4337 - 4349

Published: Nov. 28, 2024

Language: Английский

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