Liver tumour immune microenvironment subtypes and neutrophil heterogeneity

Nature, Journal Year: 2022, Volume and Issue: 612(7938), P. 141 - 147

Published: Nov. 9, 2022

Language: Английский

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Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 78(4), P. 770 - 782

Published: Jan. 26, 2023

Language: Английский

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Spatial biology of cancer evolution

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 24(5), P. 295 - 313

Published: Dec. 9, 2022

Language: Английский

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Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: July 7, 2022

The development of combination immunotherapy based on the mediation regulatory mechanisms tumor immune microenvironment (TIME) is promising. However, a deep understanding immunology must involve systemic environment (STIE) which was merely illustrated previously. Here, we aim to review recent advances in single-cell transcriptomics and spatial for studies STIE, TIME, their interactions, may reveal heterogeneity responses as well dynamic changes essential treatment effect. We evidence from preclinical clinical related significance overall survival, through different immunomodulatory pathways, such metabolic neuro-immunological pathways. also evaluate interactions after local radiotherapy or combined immunotherapy. focus our lung cancer, hepatocellular carcinoma, nasopharyngeal aiming reshape STIE TIME enhance efficacy.

Language: Английский

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An invasive zone in human liver cancer identified by Stereo-seq promotes hepatocyte–tumor cell crosstalk, local immunosuppression and tumor progression

Cell Research, Journal Year: 2023, Volume and Issue: 33(8), P. 585 - 603

Published: June 19, 2023

Abstract Dissecting and understanding the cancer ecosystem, especially that around tumor margins, which have strong implications for cell infiltration invasion, are essential exploring mechanisms of metastasis developing effective new treatments. Using a novel border scanning digitization model enabled by nanoscale resolution-SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq), we identified 500 µm-wide zone centered in patients with liver cancer, referred to as “the invasive zone”. We detected immunosuppression, metabolic reprogramming, severely damaged hepatocytes this zone. also subpopulation increased expression serum amyloid A1 A2 (referred collectively SAAs) located close on paratumor side. Overexpression CXCL6 adjacent malignant cells could induce activation JAK-STAT3 pathway nearby hepatocytes, subsequently caused SAAs’ overexpression these hepatocytes. Furthermore, secretion SAAs lead recruitment macrophages M2 polarization, further promoting local potentially resulting progression. Clinical association analysis additional five independent cohorts primary secondary ( n = 423) showed had worse prognosis. Further vivo experiments using mouse models situ confirmed knockdown genes encoding decreased macrophage accumulation delayed growth. The identification characterization human not only add an important layer regarding invasion metastasis, but may pave way therapeutic strategies advanced other solid tumors.

Language: Английский

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Pan-cancer spatially resolved single-cell analysis reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 13, 2023

Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population that plays crucial role in remodeling the tumor microenvironment (TME). Here, through integrated analysis of spatial and single-cell transcriptomics data across six common cancer types, we identified four distinct functional subgroups CAFs described their distribution characteristics. Additionally, RNA sequencing (scRNA-seq) from three additional types two newly generated scRNA-seq datasets rare namely epithelial-myoepithelial carcinoma (EMC) mucoepidermoid (MEC), expanded our understanding CAF heterogeneity. Cell-cell interaction conducted within context highlighted pivotal roles matrix (mCAFs) angiogenesis inflammatory (iCAFs) shaping immunosuppressive microenvironment. In patients with breast (BRCA) undergoing anti-PD-1 immunotherapy, iCAFs demonstrated heightened capacity facilitating proliferation, promoting epithelial-mesenchymal transition (EMT), contributing to establishment an Furthermore, scoring system based on showed significant correlation immune therapy response melanoma patients. Lastly, provided web interface ( https://chenxisd.shinyapps.io/pancaf/ ) for research community investigate pan-cancer.

Language: Английский

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Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 18, 2023

The spatial organization of the tumor microenvironment has a profound impact on biology and therapy response. Here, we perform an integrative single-cell transcriptomic analysis HPV-negative oral squamous cell carcinoma (OSCC) to comprehensively characterize malignant cells in core (TC) leading edge (LE) transcriptional architectures. We show that TC LE are characterized by unique profiles, neighboring cellular compositions, ligand-receptor interactions. demonstrate gene expression profile associated with is conserved across different cancers while tissue specific, highlighting common mechanisms underlying progression invasion. Additionally, find our signature worse clinical outcomes improved prognosis multiple cancer types. Finally, using silico modeling approach, describe spatially-regulated patterns development OSCC predictably drug Our work provides pan-cancer insights into interactive atlases ( http://www.pboselab.ca/spatial_OSCC/ ; http://www.pboselab.ca/dynamo_OSCC/ ) can be foundational for developing novel targeted therapies.

Language: Английский

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Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 23, 2023

Abstract Diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) are the most lethal brain tumors that primarily occur in pediatric adult patients, respectively. Both exhibit significant heterogeneity, shaped by distinct genetic/epigenetic drivers, transcriptional programs including RNA splicing, microenvironmental cues glioma niches. However, spatial organization of cellular states niche-specific regulatory remain to be investigated. Here, we perform a profiling DMG GBM combining short- long-read transcriptomics, single-cell transcriptomic datasets. We identify clinically relevant programs, isoform diversity, multi-cellular ecosystems across different find while tumor core enriches for oligodendrocyte precursor-like cells, radial glial stem-like (RG-like) cells enriched neuron-rich invasive niche both GBM. Further, RG-like functionally confirm FAM20C mediates growth microenvironment human neural stem cell derived orthotopic model. Together, our results provide blueprint understanding architecture vulnerabilities

Language: Английский

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Spatially resolved transcriptomics: a comprehensive review of their technological advances, applications, and challenges

Journal of genetics and genomics/Journal of Genetics and Genomics, Journal Year: 2023, Volume and Issue: 50(9), P. 625 - 640

Published: March 27, 2023

The ability to explore life kingdoms is largely driven by innovations and breakthroughs in technology, from the invention of microscope 350 years ago recent emergence single-cell sequencing, which scientific community has been able visualize at an unprecedented resolution. Most recently, Spatially Resolved Transcriptomics (SRT) technologies have filled gap probing spatial or even three-dimensional organization molecular foundation behind mysteries life, including origin different cellular populations developed totipotent cells human diseases. In this review, we introduce progress challenges on SRT perspectives bioinformatic tools, as well representative applications. With currently fast-moving promising results early adopted research projects, can foresee bright future such new tools understanding most profound analytical level.

Language: Английский

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Reconstruction of the tumor spatial microenvironment along the malignant-boundary-nonmalignant axis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 20, 2023

Abstract Although advances in spatial transcriptomics (ST) enlarge to unveil landscape of tissues, it remains challenging delineate pathology-relevant and cellular localizations, interactions exclusive a niche (e.g., tumor boundary). Here, we develop Cottrazm, integrating ST with hematoxylin eosin histological image, single-cell the boundary connecting malignant non-malignant cell spots deconvolute cell-type composition at location, reconstruct type-specific gene expression profiles sub-spot level. We validate performance Cottrazm along malignant-boundary-nonmalignant axis. identify specific macrophage fibroblast subtypes localized around that interacted cells generate structural boundary, which limits T infiltration promotes immune exclusion microenvironment. In this work, provides an integrated tool framework dissect microenvironment facilitates discovery functional biological insights, thereby identifying therapeutic targets oncologic datasets.

Language: Английский

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